Feng Gai

Photo: 
First Name: 
Feng
Last Name: 
Gai
Official Title: 
Edmund J. and Louise W. Kahn Endowed Term Professor of Chemistry
Contact Information
Office Location: 
254N
Email: 
gai@sas.upenn.edu
Phone: 
(215) 573-6256
Admin Support: 
Education: 

 

  • B.S. Peking University (1983)
  • M.S. Peking University (1986)
  • Ph.D. Iowa State University (1994)
  • Lecturer, Tsinghua University (1986-89)
  • Postdoctoral Research Associate, Harvard University (1994-97)
  • Director’s Postdoctoral Fellow, Los Alamos National Laboratory (1997-99)
Research Interests: 

 

The focus of our research is to study how proteins fold from random or quasi-random coils to their biologically functional conformations. We are particularly interested in the kinetic aspects of the folding mechanisms. Novel laser spectroscopic methods are being used and developed to study the early folding events and folding intermediates.

Fast events in protein folding

 

Understanding how folding proceeds at early time is apparently essential to the elucidation of the entire folding mechanism. To access and characterize the early folding events requires a fast initiation method and a probe that has structural specificity. Our general approach is to use novel laser-induced temperature-jump and fast-mixing techniques to initiate refolding/unfolding on nanosecond or microsecond timescales, and use time-resolved infrared and fluorescence spectroscopies to probe the subsequent folding dynamics and structural ordering along the folding/unfolding pathways. This approach provides not only fast time resolution, but also the necessary structural sensitivity, since both infrared and fluorescence are well-established conformation probes. Recent works involve the study of the helix-coil transition, helix-helix interaction, and ß-sheet formation. 

 

 

 

Single-molecule study of protein conformation dynamics

Recently, a new view of the kinetics of protein folding has emerged based on the new conceptual framework of statistical mechanical models, replacing the pathway concept with the broader notion of rugged energy landscapes. The heterogeneity in folding kinetics therefore can be realized as a result of the motions of an ensemble of protein conformations on the rugged energy hypersurface that is biased towards the native state, analogous to parallel diffusion-like processes. Studying folding dynamics statistically using single-molecule techniques will provide unique information regarding a protein's folding energy landscape, which may not be obtained by conventional ensemble studies since the conventional measurements of molecular dynamics in the condensed phase represent only averages over large numbers of molecules and events. Currently, confocal fluorescence spectroscopy and microscopy are being used to study protein spontaneous fluctuation and folding dynamics at single-molecule level. 

Selected Publications: 

 

S. Mukherjee, P. Chowdhury and F. Gai, “Infrared study of the effect of hydration on the amide I band and aggregation properties of helical peptides,” J. Phys. Chem. B 2007, 111, 4596.

 

Y. Xu, P. Purkayastha, and F. Gai, “Nanosecond folding dynamics of a three-stranded beta-sheet,” J. Am. Chem. Soc. 2006, 128, 15836.

 

M. R. Bunagan, L. Cristian, W. F. DeGrado, and F. Gai, “Truncation of a cross-linked GCN4-p1 coiled-coil leads to ultrafast folding,” Biochemistry 2006, 45, 10981.

 

D. Du, and F. Gai, “Understanding the folding mechanism of alpha-helical hairpin. Biochemistry 2006, 45, 13131.

 

M. J. Tucker, J. Tang, and F. Gai, “Probing the kinetics of membrane-mediated helix folding,” J. Phys. Chem. B 2006, 110, 8105.

 

M. J. Tucker, R. Oyola, and F. Gai, “Conformational distribution of a 14-residue peptide in solution: a FRET study,” J. Phys. Chem. B 2005, 109, 4788.

 

D. G. Du, Y. J. Zhu, C-Y. Huang, and F. Gai, “Understanding the key factors that control the rate of -hairpin folding,” Proc. Natl. Acad. Sci. USA 2004, 101, 15915.

 

Y. J. Zhu, D. O. V. Alonso, K. Maki, C-Y Huang, S. J. Lahr, V. Daggett, H. Roder, W. F. DeGrado, and F. Gai, “Ultrafast folding of alpha3D, a de novo designed three-helix bundle protein,” Proc. Natl. Acad. Sci. USA 2003, 100, 15486.

 

Z. Getahun, C-Y. Huang, T. Wang, B. D. León, W. F. DeGrado, and F. Gai, “Using nitrile-derivatized amino acids as infrared probes of local environment,” J. Am. Chem. Soc. 2003, 125, 405.

 

C.-Y. Huang, Z. Getahun, Y. J. Zhu, J. W. Klemke, W. F. DeGrado, and F. Gai, “Helix formation via conformation diffusion search,” Proc. Natl. Acad. Sci. USA 2002, 99, 2788.

Michael Fryd

Photo: 
First Name: 
Michael
Last Name: 
Fryd
Official Title: 
Adjunct Professor of Chemistry

Organic and Polymer Chemistry

Contact Information
Office Location: 
Senior Faculty Suite
Email: 
mfryd@sas.upenn.edu
Research Interests: 

Synthetic methods, with special emphasis on living or controlled polymerization, are used to design polymers with unique architectures such as telechelic polymers, stars, and block or graft copolymers. We study the self assembly of these polymers both in solution and the solid state, and use them in the synthesis of organic and inorganic nanoparticles, and in a variety of material applications such as membranes, sensors, microelectronic devices, and drug delivery systems.

Selected Publications: 

 

Peng, C.-H.; Fryd, M.; Wayland, B. B. "Organocobalt Mediated Radical Polymerization of Acrylic Acid in Water" Macromolecules ACS ASAP 

 

Xu, C.; Fu, X.; Fryd, M.; Xu, S.; Wayland, B. B.; Winey, K. I.; Composto, R. J. "Reversible Stimuli-Responsive Nanostructures Assembled from Amphiphilic Block Copolymers" Nano Letters 6, 282-287 (2006).

 

Xu, C.; Wayland, B. B.; Fryd, M.; Winey, K. I.; Composto, R. J. "pH-Responsive Nanostructures Assembled from Amphiphilic Block Copolymers" Macromolecules 39, 6063-6070 (2006).

 

Wayland, B. B.; Peng, C.-H.; Fu, X.; Lu, Z.; Fryd, M. "Degenerative Transfer and Reversible Termination Mechanisms for Living Radical Polymerizations Mediated by Cobalt Porphyrins" Macromolecules 39, 8219-8222 (2006).

 

Fryd, M.; Grushin, V.; Herron, N.; Periyasamy, M.; Petrov, V. A.; Radu, N. S. "Polymers having attached luminescent metal complexes and devices made with such polymers" US Patent 7,060,372, 2006.

 

Fryd, M.; Periyasamy, M.; Schadt, F. L., III "Polymers for photoresist compositions for microlithography" WO Patent 6,951,705, 2005.

 

Lu, Z.; Fryd, M.; Wayland, B. B. "New Life for Living Radical Polymerization Mediated by Cobalt(II) Metalloradicals" Macromolecules 37, 2686-2687 (2004).

 

Fryd, M.; Schadt, F. L., III; Periyasamy, M. "Nitrile/Fluoroalcohol-containing Photoresists and Associated Processes for Microlithography" US Patent 6, 503, 686, 2003.

 

Berge, C. T.; Fryd, M.; Johnson, J. W.; Moad, G.; Rizzardo, E.; Scopazzi, C.; Thang, S. H. "Process for Preparing Star Shaped Microgels from Macromonomers with Terminal Ethylenic Unsaturation" US Patent 6, 653, 407, 2003.

 

Ma, S.-H.; Fryd, M. "Process for Making Printed Images Using Pigmented Ink Jet Compositions" US Patent 6, 117, 921, 2000

Donald D. Fitts

Photo: 
First Name: 
Donald D.
Last Name: 
Fitts
Official Title: 
Emeritus Professor of Chemistry

Physical Chemistry

Contact Information
Office Location: 
Senior Faculty Suite
Email: 
dfitts@sas.upenn.edu
Phone: 
(215) 898-8628
Education: 
  • A.B. Harvard University (1954)
  • Ph.D. Yale University (1957)
  • N.S.F. Postdoctoral Fellow, University of Amsterdam (1957-58)
  • NATO Senior Science Fellow, Imperial College, University of London (1971)
  • Academic Visitor, Oxford University (1978)
  • Associate Dean for Graduate Studies, School of Arts and Sciences (1978-82, 83-94)
  • Acting Dean, School of Arts and Sciences (1982-83)
  • Visiting Fellow, Corpus Christi College, Cambridge and Visiting Scholar, Department of Chemistry, University of Cambridge, U.K. (1996)
Research Interests: 

From a knowledge of the interactions among molecules, it is possible in principle to predict the structure and the thermodynamic properties of materials as well as the dynamics of molecular processes. The overall objective of our research program is twofold: to evaluate the potential energies of intermolecular interactions for various systems as accurately as possible and to study by means of statistical mechanics the influence of these potentials of intermolecular force on the structure and properties of macroscopic systems.

Zahra Fakhraai

Photo: 
First Name: 
Zahra
Last Name: 
Fakhraai
Official Title: 
Associate Professor of Chemistry

Physical Chemistry, Materials Chemistry, Nanoscale Science and Engineering

Contact Information
Email: 
fakhraai@sas.upenn.edu
Admin Support: 
Education: 
  • B.Sc. Physics, Sharif University of Technology, Iran 1999
  • M. Sc. Physics, Sharif University of Technology, Iran 2001
  • Ph.D. Physics, University of Waterloo, 2007
  • Post-Doctoral associate, Chemistry, University of Toronto, 2007-08.
  • NSERC Post-Doctoral Fellow, Chemistry, University of Wisconsin-Madison, 2009-11.
Research Interests: 

Our group is interested to study the effect of nano-confinement on structure, dynamics and other properties of materials. Materials behave differently on surfaces, interfaces or small length scales compared to their bulk properties.  Understanding such differences are crucial in many technological applications where materials are constrained in nanometer size spaces, such as organic electronics, polymer applications and drug delivery. One can take advantage of such difference to produce novel materials, such asexceptionally stable glasses or harvest light for various applications. In biological systems, most of the dynamics happens in nanometer size proximity of surfaces and interfaces, and understanding the properties in confinement is a key in predicting function. We focus our efforts on understanding the origins of such modified properties on a fundamental level as well as possible application of such phenomena in producing novel materials or experimental tools.


Enhanced Mobility at the Surface of Polymeric and Organic Glasses: 

 

We study the properties of glasses at the air/glass interface. Our studies show that below the glass transition temperature, where the bulk of the material is in an out of equilibrium state, the interfacial dynamics are many orders of magnitude faster that the bulk dynamics. As a result a layer close to the interface maintains equilibrium properties. We study the dynamics of this layer, its thickness, and its effect on the properties of the underlying glass. The interfacial layer can strongly modify properties of amorphous materials in nanometer length scales. They also allow one to produce near-equilibrium structures at temperatures well below bulk glass transition temperature, through physical vapor deposition.


Exceptionally Stable Glasses: 


 

The enhanced mobility of the interfacial layer allows us to produce near-equilibrium glasses at temperatures well below the bulk glass transition temperature, Tg, by means of physical vapor deposition (PVD). Exceptionally stable glasses are formed when the substrate temperature during PVD is maintained just below the glass transition temperature. We study the morphology and the kinetics of PVD films during formation and their relationship to the final properties of the stable glass. These studies provide information on mechanisms of rapid aging below Tg and stable glass formation. We also investigate exceptional material properties of these glasses and the role of the chemical structure in these properties such as the optical birefringence and electronic properties.


 

Novel Emergent Optical Properties in Disordered Nanoparticle Clusters: 


 

Using simple synthetic routs we can produce dielectric core-gold shell nanoparticles decorated with randomly packed nanoparticles of various shapes and sizes. Spiky nanoparticles are a good example of such nanoparticles. Broadband and tunable structure of spiky gold nanoshells makes them ideal for various applications such as enhanced Raman scattering, temperature and index sensing and sensors for biological and light harvesting applications. Exceptional properties, such as higher order quadrupoloar scattering and magnetic dipole plasmons in these nanoparticles are due to inherent disorder in their structure and random packing arrangements. We explore optical properties of these nanoshells, using various theoretical and experimental tools. We also develop new techniques that allow us to study properties of meta materials formed from these types of particles.

 


Surface Mediated Self-assembly of Amyloid Aggregrates: 


 

Surface self-assembly provides an alternative pathway for amyloid aggregation that is not available in bulk solutions. We us high-resolution atomic force microscopy and other imaging techniques to study the adhesion and diffusion of peptides on various surfaces and their role in facilitating amyloid fibril formation through self-assembly routs. We also use our exceptional capabilities in high-resolution imaging to study the conformation of amyloids formed under various conditions in aqueous conditions.

Selected Publications: 

1.     T. Liu, K. Cheng, E. Salami, F. Gao, C. Li, X. Tong, Y. Lin, Y. Zhang, W. Zhang, L. Klinge, P. Walsh and Z. Fakhraai, "The effect of chemical structure on the stability of physical vapor deposited glasses of 1,3,5-triarylbenzene"J. Chem. Phys. 143, 084506 (2015). 

2.     Z. Qian, S.P. Hastings, C. Li, B. Edward, C.K. McGinn, N. Engheta, Z. Fakhraai* and S.J. Park, "Raspberry-like Metamolecules Exhibiting Strong Magnetic Resonances",  ACS Nano9, 1263-1270 (2015). 

3.     E. Glor, and Z. Fakhraai, "Facilitation of Interfacial Dynamics in Entangled Polymer Films", J. Chem. Phys. 141, 194505 (2014).

4.     Y. Lin, E.J. Peterson, and Z. Fakhraai, "Surface Effects Mediate Self-Assembly of Amyloid-β Peptides"ACS Nano8, 10178-10186 (2014).

5.     S. P. Hastings, P. Swanglap, Z. Qian, Y. Fang, S.J. Park, S. Link, N. Engheta, and Z. Fakhraai, "Quadrupole-Enhanced Raman Scattering", ACS Nano,  8 , 9025-9034 (2014).

6.     B. Sanchez-Gaytan, Z. Qian, S. Hastings, M. Reca, Z. Fakhraai, and S. J. Park, “Controlling
the Topography and Surface Plasmon Resonance of Gold Nanoshells by a Templated Surfactant-Assisted Seed Growth Method
 ”, J. Phys. Chem. C. 117, 8916-8923 (2013).

7.     C. R. Daley, Z. Fakhraai, M. D. Ediger, and J. A. Forrest, “Comparing Surface and Bulk Flow of a Molecular Glass Former”, Soft Matter, 8, 2206-2212 (2012). 

8.     M. Paulite, Z. Fakhraai, N. Gunari, A. Tanur, and G. C. Walker, “Imaging Secondary Structure of Individual Amyloid Fibrils of a β(2)-Microglobulin Fragment Using Near-Field Infrared Spectroscopy”, J. Am. Chem. Soc. 133, 7376-7383 (2011).

9.     Z. Fakhraai and J. A. Forrest, “Measuring the Surface Dynamics of Glassy Polymers”, Science, 319, 600- 604 (2008).

10.  Z. Fakhraai, and J. A. Forrest, “Probing Slow Dynamics in Supported Thin Polymer Films”, Phys. Rev. Lett. 95, 025701(2005).

Ivan J. Dmochowski

Photo: 
First Name: 
Ivan J.
Last Name: 
Dmochowski
Official Title: 
Professor of Chemistry

Bioinorganic, Bioorganic, Biophysical Chemistry

Additional Titles: 
Undergraduate Chair
Contact Information
Office Location: 
348 N, Lab: 332, 334, 336, 338 N
Email: 
ivandmo@sas.upenn.edu
Phone: 
215-898-6459
Twitter: 
@DmochowskiUPenn
Admin Support: 
Education: 
  • B.A. Harvard College (1994)
  • Research Fellow, Johannes Gutenberg Universitaet, Mainz, DE (1994-1995)
  • Ph.D. California Institute of Technology (2000)
  • Caltech Herbert Newby McCoy Award (2000)
  • Helen Hay Whitney Postdoctoral Fellow, Biophysics, Caltech (2000-2002)
  • Camille and Henry Dreyfus New Faculty Award (2003)
  • National Science Foundation CAREER Award (2005)
  • Camille and Henry Dreyfus Teacher-Scholar Award (2007)
Research Interests: 

Our lab is developing chemical and biophysical tools to study and manipulate complex biological systems. Projects span many areas of synthetic organic, inorganic, and biophysical chemistry; molecular, cell, and developmental biology; and bioengineering. We are particularly interested in developing new technologies for biomolecular imaging and the fabrication of functional bio-nanomaterials.

Hyperpolarized 129Xe Biosensors for Early Cancer Detection

Molecular imaging technologies hold great promise for early cancer diagnosis and intervention. Our goal is to develop new reagents that extend the capabilities of magnetic resonance imaging (MRI) for monitoring multiple cancer markers simultaneously in vivo. 129Xe has found increasing use for biological imaging applications, due to its biological compatibility (xenon is an anesthetic at high concentrations), hyperpolarizability (this enhances signals 1,000-fold), and high affinity for organic cages such as cryptophanes. The chemical shift of 129Xe varies by a remarkable 200 ppm, depending on its molecular environment: Thus, a 129Xe atom encapsulated inside a cryptophane is a sensitive reporter of perturbations outside the cage. Based on this principle, our lab is generating new biosensors that will identify biomarkers associated with cancers of the breast, lungs, brain, and pancreas. The long-range goal of this project is to use MRI to detect aberrant proteins that cause cancer in humans, years before the formation of a tumor.

Ferritin Templates for Nanoparticle Synthesis and Assembly

The goal of this project is to use ferritin proteins as templates for synthesizing and assembling inorganic nanoparticles with nanometer precision. Ferritins contain 24 four-helix bundle subunits that self-assemble to create a large central cavity. We have made water-stable, 10-12-nm gold and silver nanoparticles inside ferritin (gray sphere). Particles are fully characterized using facilities at the UPenn Laboratory for Research on the Structure of Matter (LRSM). We are functionalizing the surface of these ferritin-metal nanoparticles for sensing and nano/biomaterials applications. We are also performing computational protein design, in collaboration with the Saven lab, to mutate residues inside the ferritin cavity to enhance their metal-binding properties. Methods for organizing ferritin metal nanoparticles in 2- and 3-dimensions are being developed, in order to build very small conducting circuits. 

Laser-Activated Chemical Biology: Controlling Genes with Light

The goal of this project is to develop methods for turning genes "on" and "off" with light inside neurons and developing zebrafish embryos with high spatial and temporal control. As a first step, we have developed methods for incorporating a photoactive blocking group in the middle of a DNA or RNA oligonucleotide. In one application, we modulated primer extension by DNA polymerase (KF) using UV light. Photoactivation was monitored using a fluorescent reporter. We are now developing methods to control protein translation by the ribosome using similarly caged RNA. Blocking groups mask the messenger RNA start codon, and are designed to prevent translation until photocleavage. We will control complex gradients of proteins involved in cell signaling during zebrafish development and wound healing, using a state-of-the-art UV confocal microscope in the lab.

Selected Publications: 

 

X. Tang, J. Swaminathin, A.M. Gewirtz, I.J. Dmochowski, Regulating gene expression in human leukemia cells using light-activated oligodeoxynucleotides, Nucl. Acids Res. (36) 559-569, 2008.

 

J.A. Aaron, J.M. Chambers, K.M. Jude, L. Di Costanzo, I.J. Dmochowski, D.W. Christianson, Structure of a 129Xe-cryptophane biosensor complexed with human carbonic anhydrase II, J. Am. Chem. Soc. (130) 6942-6943, 2008.

 

G.K. Seward, Q. Wei, I.J. Dmochowski, Peptide-mediated cellular uptake of cryptophane, Bioconjug. Chem. (19) 2129-2135, 2008.

 

J.L. Richards, X. Tang, A. Turetsky, I.J. Dmochowski, RNA bandages for photomodulating in vitro protein synthesis, Bioorg. Med. Chem. Lett. (18) 6255-6258, 2008.

 

C. Butts, J. Swift, S.-G. Kang, L. Di Costanzo, D.W. Christianson, J.G. Saven, I.J. Dmochowski, Directing noble metal ion chemistry within a designed ferritin protein, Biochemistry (47) 12729-12739, 2008.

 

J.L. Chambers, P.A. Hill, J.A. Aaron, Z. Han, D.W. Christianson, N.N. Kuzma, I.J. Dmochowski, Cryptophane xenon-129 nuclear magnetic resonance biosensors targeting human carbonic anhydrase, J. Am. Chem. Soc. (131) 563-569, 2009.

 

P.A. Hill, Q. Wei, T. Troxler, I.J. Dmochowski, Substituent effects on xenon binding affinity and solution behavior of water-soluble cryptophanes, J. Am. Chem. Soc. (131) 3069-3077, 2009.

 

G.P. Robbins, M. Jimbo, J. Swift, M.J. Therien, D.A. Hammer, I.J. Dmochowski, Photo-initiated destruction of composite porphyrin-protein polymersomes, J. Am. Chem. Soc., (131) 3872-3874, 2009. 

 

J. Swift, C. Butts, J. Cheung-Lau, V. Yerubandi, I.J. Dmochowski, Efficient self-assembly of Archaeoglobus fulgidus ferritin around metallic cores, Langmuir, (25) 5219-5225, 2009.

 

C.A. Butts, J. Xi, G. Brannigan, M.L. Klein, R.G. Eckenhoff, I.J. Dmochowski, Identification of a fluorescent general anesthetic, 1-aminoanthracene, Proc. Natl. Acad. Sci. U.S.A. (106) 6501-6506, 2009.

 

I.J. Dmochowski, Xenon out of its shell, Nature Chemistry, ‘In Your Element’ invited feature article, vol. 1, 250, June 2009.

 

O. Taratula, I.J. Dmochowski, Functionalized 129Xe contrast agents for magnetic resonance imaging, Curr. Opin. Chem. Biol. (14) 97-104, 2010.

 

J.L. Richards, G.K. Seward, Y. Huang, I.J. Dmochowski, Turning DNAzymes on and off with light, ChemBioChem (11) 320-324, 2010.

 

J. Lampe, Z. Liao, I.J. Dmochowski, P.S. Ayyaswamy, D.M. Eckmann, Imaging macromolecular interactions at an interface, Langmuir (26) 2452-2459, 2010.

Courses Taught: 
  • Chemistry 101, "General Chemistry"
  • Chemistry 559, "Biomolecular Imaging"
  • Chemistry 567, “Bioinorganic Chemistry”

William P. Dailey

Photo: 
First Name: 
William P.
Last Name: 
Dailey
Official Title: 
Associate Professor of Chemistry

Organic Chemistry

Contact Information
Office Location: 
551 N, Lab: 507 N
Email: 
dailey@sas.upenn.edu
Phone: 
(215) 898-2704
Education: 

 

  • B.S. University of Connecticut (1979)
  • Ph.D. Dartmouth College (1983)
  • Postdoctoral Fellow, Yale University (1983-85)
  • Alfred P. Sloan Research Fellow (1990-94)
  • Lindback Award for Teaching Excellence (1992)
Research Interests: 

 

For many years the Dailey group has been involved in the areas of reactive intermediates, strained-ring chemistry, computational chemistry, matrix isolation, and organo-fluorine chemistry.

More recently we have turned our attention to the study of the mechanism of anesthesia. Many of the currently used inhalation anesthetics are small fluorinated molecules. One of the currently most widely used intravenous anesthetics is Propofol, a drug which allegedly contributed to the demise of Michael Jackson. Anesthetics are some of the most dangerous drugs currently used today, and their mechanism of action (both good and bad) remains largely unknown. New photoaffinity anesthetic compounds which mimic anesthetics but which can be photoactivated so that they can bind to potential molecular targets are being developed in our group. Using these compounds we are investigating the mechanism of anesthesia in collaboration with Dr. Roderick Eckenhoff's group at the School of Medicine at Penn. This collaboration was recently highlighted in C&E News.

 

Structures of several currently used anesthetics and the corresponding photoaffinity labeling analogs prepared in our laboratory.

Selected Publications: 

 

Michael A Hall, Jin Xi, Chong Lor, Shuiping Dai, Robert Pearce, William P. Dailey, Roderic G. Eckenhoff , "AziPm, photoactive analog of the intravenous general anesthetic, propofol", J. Med. Chem., 2010, 53, 5667 - 5675. 

 

Jerome Henin, William P. Dailey, Grace Brannigan, Roderic Eckenhoff, Michael L. Klein, "An Atomistic Model for Simulations of the General Anesthetic Isoflurane", J. Phys. Chem. B. 2010, 114(1), 604 - 612.

 

Roderic G. Eckenhoff, Jin Xi, Motomu Shimaoka, Aditya Bhattacharji, Manuel Covarrubias, William P. Dailey, "Azi-isoflurane, a photolabel analog of the commonly used inhaled general anesthetic, isoflurane", ACS Chemical Neuroscience, 2010, 1, 139 - 145.

 

L. Sangeetha Vedula, Grace Brannigan, Nicoleta J. Economou, Jin Xi, Michael A. Hall, Renyu Liu, Matthew J. Rossi, William P. Dailey, Kimberly C. Grasty, Michael L. Klein, Roderic G. Eckenhoff, Patrick J. Loll, "A Unitary Anesthetic Binding Site at High Resolution" J. Biol. Chem., 2009, 284, 24176-24184.

 

Jin Xi, Renyu Liu, Matthew J. Ross, Jay Yang, Patrick J. Loll, William P. Dailey, and Roderic G. Eckenhoff, "Photoactive Analogues of the Haloether Anesthetics Provide High-Resolution Features from Low-Affinity Interactions", ACS Chem. Biol., 2006, 1 , 377-384.

 

Tomas Martinu and William P. Dailey, "On the Reactivity of 1-Chloro-3-phenyldiazirines", J. Org. Chem., 2006, 71, 5012-5015.

 

Tomas Martinu and William P. Dailey, "Synthesis of Carboalkoxychloro- and Bromodiazirines", J. Org. Chem., 2004, 69, 7359-7362.

 

Roderic G. Eckenhoff, Frank Knoll, Eric P. Greenblatt, William P. Dailey " A Photolabel Mimic for the Inhaled Haloalkane Anesthetics", J. Med. Chem., 2002, 45, 1879 - 1886.

 

Dana R. Reed, Steven R. Kass, Kathleen R. Mondanaro, William P. Dailey "Formation of 1 1-Bicyclo[1.1.1]pentyl Anion and an Experimental Determination of the Acidity and C-H Bond Dissociation Energy of 3-t-Butylbicyclo[1.1.1]pentane", J. Am. Chem. Soc., 2002; 124(11); 2790-2795.

 

T. Martinu and W.P. Dailey " Facile One-Pot Preparation of 3-Chloro-2-(chloromethyl)propene and an Ab Initio Study of the Deamination Reaction of Nitrosoaziridine", J. Org. Chem. 2000, 65(20); 6784-6786.

 

T. Hirayama et al. "Responsive-to-Antagonist, a Menkes/Wilson disease-related copper transporter, is required for ethylene signaling in Arabidopsis", Cell 1999, 97, 383-393.

 

D. L. S. Brahms and W. P. Dailey "Fluorinated Carbenes", Chem. Rev. 1996, 96, 1585-1632.

 

T. D. Golobish and W. P. Dailey "Synthesis and Structure of Bishomohexaprismanedione", Tetrahedron Lett. 1996, 37, 3239 - 3242.

 

D. L. S. Yokotsuji et al. "Generation, Direct Observation under Matrix-isolation Conditions and Ab Initio Calculations for 2-Azacyclopenta-2, 4-dien-1-one", J. Phys. Chem. 1995, 99, 15870 - 15873 .

 

C. A. Jacobs, J. C. Brahms, W. P. Dailey, K. Beran and M. D. Harmony "Synthesis, Microwave Spectrum, and Ab Initio Calculations for Difluorocyclopropenone", J. Am. Chem. Soc. 1992, 114, 115-121.

 

M. A. Forman and W. P. Dailey "The Lithium Perchlorate-Diethyl Ether Rate Acceleration of the Diels-Alder Reaction: Lewis Acid Catalysis by Lithium Ion", J. Am. Chem. Soc. 1991, 113, 2761-2762.

Courses Taught: 

 

  • Chemistry 241
  • Chemistry 242
  • Chemistry 541

Barry S. Cooperman

Photo: 
First Name: 
Barry S.
Last Name: 
Cooperman
Official Title: 
Professor of Chemistry

Biological Chemistry

Contact Information
Office Location: 
358 N, Lab: 307, 309 N
Email: 
cooprman@sas.upenn.edu
Phone: 
(215) 898-6330
Education: 
  • B.A. Columbia College (1962)
  • Ph.D. Harvard University (1968)
  • NATO postdoctoral fellow
  • Institut Pastuer, Paris (1967-68)
  • Merck Faculty Award (1970)
  • Sloan Foundation Fellow (1974-77)
  • N.I.H. Physical Biochemistry Study Section (1978-82)
  • Vice Provost for Research (1982-1995)
  • Chevalier de l’Ordre des Palmes Académique (2004)
  • Fellow of the American Association for the Advancement of Science (2004)
Research Interests: 

 

Our overall thrust is to study the linkage between biological structure and function, using a broad array of chemical, physical, and biological tools. Our major efforts fall in three principal areas.

 

Ribosomes 

We are interested in the structure and function of the bacterial ribosome, which is the site of protein biosynthesis in the cell. Most recently we have been focusing on the application of kinetic and spectroscopic approaches, including the use of single molecule and single-turnover studies in conjunction with fluorescence resonance energy transfer (FRET), to elucidate mechanisms for ribosomal catalysis of protein synthesis. We are particularly interested in the functions of G-proteins on the ribosome, and how these functions are altered by antibiotics and by mutations of tRNAs and ribosomal RNA. We are also pursuing studies on how the rate of protein synthesis is modulated by specific mRNA and oligopeptide sequences.

 

Ribonucleotide reductase (RR) 

RR catalyzes the reduction of nucleoside diphosphates to deoxynucleoside diphosphates and is the key enzyme controlling the rate of DNA synthesis. As such it is highly regulated and is a target enzyme for cancer chemotherapy. Our studies focus on the RRs derived from mammalian cells. We are developing novel and specific inhibitors of this enzyme, using both a rational design approach and combinatorial methods, and based in part on our detailed studies of the allosteric regulation of this enzyme. This work utilizes synthetic organic chemistry, biochemistry, molecular modeling and X-ray crystallography approaches.

 

Serine proteinase inhibitors ("serpins") 

Serpins are known to be of great importance for inflammation process in mammals. We seek to understand the structural basis for the specificity of interaction of these serpins with a variety of serine proteases, using a combination of chemical modification, single turnover FRET kinetics, FT-IR spectroscopy and genetic engineering approaches to elucidate the basic mechanisms underlying such specificity. A second area of interest is serpin polymerization, which underlies several diseases associated with serpin malfunction. These studies are being carried out using single molecule confocal microscopy.

 

Dynamics of Ribosomal Conformational Change

Selected Publications: 

 

Wang Y, Qin H, Kudaravalli RD, Kirillov SV, Dempsey GT, Pan D, Cooperman BS, Goldman YE (2007) Single Molecule Structural Dynamics of EF-G·Ribosome Interaction During Translocation, Biochemistry. in press

 

Grigoriadou C, Marzi S, Pan D, Gualerzi CO, Cooperman BS (2007) The Translational Fidelity Function of IF3 During the Transition from 30S to 70S Initiation Complex. J. Mol. Biol., in press, doi:10.1016/j.jmb.2007.07.031

 

Grigoriadou C, Marzi S, Kirillov S, Gualerzi CO, Cooperman BS (2007) A Quantitative Kinetic Scheme for 70S Translation Initiation Complex Formation. J. Mol. Biol., in press,

doi:10.1016/j.jmb.2007.07.032

 

Chowdhury P, Wang W, Bunagan MR, Klemke JW, Tang J, Lavender S, Saven JG, Cooperman BS, Gai F (2007) Fluorescence Correlation Spectroscopic Study of Serpin Depolymerization by Computationally Designed Peptides. J Mol Biol. 369, 462-73.

 

Pan D, Kirillov S, Cooperman BS (2007) Kinetically Competent Intermediate(s) in the Translocation Step of Protein Synthesis. Molecular Cell,. 25, 519-529.

 

Pan D, Kirillov S, Zhang CM, Hou YM, Cooperman BS (2006) Rapid Ribosomal Translocation Depends on the Conserved 18:55 Base Pair in P-site tRNA. Nature Structural and Molecular Biology, 13, 354-9.

 

Seo HS, Abedin S, Kamp D, Wilson DN, Nierhaus KH, Cooperman BS (2006) EF-G Dependent GTPase on the Ribosome. Conformational Change and Fusidic Acid Inhibition. Biochemistry 45, 2504-14.

 

He J, Roy B, Perigaud C, Kashlan OB, Cooperman BS (2005) The enantioselectivities of the active and allosteric sites of mammalian ribonucleotide reductase. FEBS J. 272,1236-42. 

 

Gao Y, Kashlan OB, Kaur J, Tan C, Cooperman BS (2005) Mechanisms of action of peptide inhibitors of mammalian ribonucleotide reductase targeting quaternary structure. Biopolymers (Peptide Science), 80, 9-17.

 

Purkayastha P, Klemke JW, Lavender S, Oyola R Cooperman BS, Gai F (2005) α1-Antitrypsin polymerization: A fluorescence correlation spectroscopic study. Biochemistry, 44, 2642-2649.

 

Seo HS, Kiel M, Pan D, Raj VS, Kaji A Cooperman BS (2004) Kinetics and Thermodynamics of RRF, EF-G, and Thiostrepton Interaction on the E. coli Ribosome. Biochemistry 43, 12728-40.

 

Tan C, Gao Y, Kaur J, Kashlan, O. B., Cooperman BS (2004) More potent linear peptide inhibitors of mammalian ribonucleotide reductase. Bioorg. Med. Chem. Lett., 14, 5301-5304.

 

Kashlan OB, Cooperman BS (2003) Comprehensive model for allosteric regulation of mammalian ribonucleotide reductase: refinements and consequences. Biochemistry. 42(6): 1696-1706.

 

Gao Y, Liehr S, Cooperman BS (2002) Affinity-Driven Selection of Tripeptide Inhibitors of Ribonucleotide Reductase. Bioorg. Med. Chem. Lett., 12, 513-515.

 

Hsieh MC, Cooperman BS (2002) The Inhibition of Prostate-Specific Antigen (PSA) by a-Antichymotrypsin: Salt-Dependent Activation Mediated by a Conformational Change. Biochemistry 41, 2990-2997.

 

Kashlan OB, Scott CP, Lear JD, Cooperman BS (2002) A Comprehensive Model for the Allosteric Regulation of Mammalian Ribonucleotide Reductase. Functional Consequences of ATP- and dATP-Induced Oligomerization of the Large Subunit. Biochemistry 41, 462-474.

 

Scott CP, Kashlan OB, Lear JD, Cooperman BS (2001) A Quantitative Model for Allosteric Control of Purine Reduction by Murine Ribonucleotide Reductase. Biochemistry 40, 1651-1661.

 

O’Malley KM, Cooperman BS (2001) Formation of the covalent chymotrypsin: antichymotrypsin complex involves no large-scale movement of the enzyme. J. Biol. Chem., 276, 6631-6637.

 

Pender BA, Wu X, Axelsen PH, Cooperman BS (2001) Toward a Rational Design of Peptide Inhibitors of Ribonucleotide Reductase: Structure - Function and Modeling Studies. J. Med. Chem., 44, 36-46.

David W. Christianson

Photo: 
First Name: 
David W.
Last Name: 
Christianson
Official Title: 
Roy and Diana Vagelos Professor in Chemistry and Chemical Biology

Biological Chemistry

Contact Information
Office Location: 
2001 IAST, Lab: 2070 IAST
Email: 
chris@sas.upenn.edu
Phone: 
(215) 898-5714
Admin Support: 
Education: 
  • A.B. Harvard College (1983)
  • A.M. Harvard University (1985)
  • Ph.D. Harvard University (1987)
  • Searle Scholar Award (1989–1992)
  • Young Investigator Award, Office of Naval Research (1989–1992)
  • Alfred P. Sloan Foundation Research Fellow (1992–1994)
  • Camille and Henry Dreyfus Teacher-Scholar Award (1993–1994)
  • Pfizer Award in Enzyme Chemistry, American Chemical Society (1999)
  • Fellow in Natural Sciences (Chemistry), Sidney Sussex College, University of Cambridge (2006)
  • Underwood Fellowship, Department of Biochemistry, University of Cambridge (2006–2007)
  • Senior Fellow, American Asthma Foundation (2006)
  • Fellow of the John Simon Guggenheim Memorial Foundation (2006–2007)
  • National Academies Board on Chemical Sciences and Technology (2011–2017)
  • The Repligen Award in Chemistry of Biological Processes, American Chemical Society (2013)
  • Fellow of the Royal Society of Chemistry (London) (2013)
  • Elizabeth S. and Richard M. Cashin Fellow, Radcliffe Institute for Advanced Study, Harvard University
  • Visiting Professor of Chemistry and Chemical Biology, Harvard University
Research Interests: 

We are interested in structural aspects of the mechanisms of hydrolytic metalloenzymes in the arginase-deacetylase family. To date, we have determined the crystal structures of rat arginase I, human arginase I, human arginase II, and arginases from Plasmodium falciparum, Leishmania mexicana, and Schistosoma mansoni. Structural and enzymological data suggest a mechanism for arginine hydrolysis in which both manganese ions activate a bridging hydroxide ion for nucleophilic attack at the guanidinium group of arginine in the first step of catalysis. Based on our structural and mechanistic analyses, we designed and synthesized boronic acid analogues of arginine such as 2-amino-6-boronohexanoic acid (ABH, Kd = 5 nM) [Baggio et al. (1997) J. Am. Chem. Soc. 119, 8107]. The boronic acid moiety of ABH similarly undergoes nucleophilic attack by the metal-bridging hydroxide ion to yield a metal-bound boronate anion that mimics the tetrahedral intermediate and its flanking transition states in catalysis (Figure 1), as shown in X-ray crystallographic studies of rat arginase I [Cox et al. (1999) Nature Struct. Biol. 6, 1043], human arginase I [Di Costanzo et al. (2005) Proc. Natl. Acad. Sci. USA, 102, 13058], P. falciparum arginase [Dowling et al. (2010) Biochemistry 49 5600], and L. mexicana arginase [D' Antonio et al. (2013) Arch. Biochem. Biophys. 535, 163]

Figure 1: Human arginase I-ABH complex. (a) Omit electron density map of ABH bound in the enzyme active site at 1.29 Å resolution. Water molecules appears as red spheres and Mn(II) ions appears as larger pink spheres. (b) Summary of arginase-ABH interactions; manganese coordination interactions are designated by green dashed lines, and hydrogen bonds are indicated by black dashed lines. (c) Stabilization of the tetrahedral intermediate (and flanking transition states) in the arginase mechanism based on the binding mode of ABH.

 

We have also used ABH as a chemical tool for probing the role of arginase in regulating arginine bioavailability for nitric oxide (NO) biosynthesis in tissues and in live animals. We discovered that arginase inhibition by ABH enhances smooth muscle relaxation in ex vivo organ bath studies. Since smooth muscle relaxation in the corpus cavernosum of the penis is necessary for erection, we concluded that human penile arginase is a potential target for the development of new therapies in the treatment of erectile dysfunction [Cox et al. (1999) Nature Struct. Biol. 6, 1043]. Our subsequent in vivo studies demonstrated that arginase inhibition by ABH enhances erectile function and vasocongestion in the male and female genitalia, so we concluded that both male erectile dysfunction and female sexual arousal disorder are potentially treatable by ABH [Cama et al. (2003) Biochemistry 42, 8445; Christianson (2005) Acc. Chem. Res. 38, 191]. More recent studies show that ABH may also be useful in the treatment of certain cardiovascular disorders such as atherosclerosis [Santhanam et al. (2007) Circulation Res. 101, 692; Ryoo et al. (2008) Circulation Res. 102, 923]. The biopharmaceutical company Arginetix was founded in 2008 based on our arginase inhibitor technology.

 

Our work with metal-dependant histone deacetylases recently yielded the first crystal structure of a histone deacetylase complexed with a macrocyclic depsipeptide inhibitor (Figure 2) [Cole et al. (2011) J. Am. Chem. Soc. 133, 12474]. Additionally, we recently showed that mutations in histone deacetylase 8 identified in patients diagnosed with Cornelia de Lange Syndrome compromise catalytic activity by causing structural changes in the active site that perturb substrate binding and catalysis [Deardorff et al. (2012) Nature 489, 313; Decroos et al. (2014) ACS Chem. Biol., in press.]. In addition to our work with arginase, we are studying other metalloenzymes that adopt the arginase fold, such as polyamine deacetylase [Lombardi et al. (2011) Biochemistry 50, 1808].

 

In other metalloenzyme work, we have determined the crystal structure of A. aeolicus LpxC, a zinc-requiring enzyme that catalyzes the first step of lipid A biosynthesis in Gram-negative bacteria [Whittington et al. (2003) Proc. Natl. Acad. Sci. USA 100, 8146] (Figure 3). Subsequent structural studies have allowed us to pinpoint regions of the active site that interact with the fatty acid and diphosphate moieties of the substrate [Gennadios et al. (2006) Biochemistry 45, 7940; 15216], and these studies have guided the first steps in the structure-based design of new LpxC inhibitors that may ultimately be useful in the treatment of Gram-negative bacterial infections [Shin et al. (2007) Bioorg. Med. Chem. 15, 2617]. To date, we have broadened these structural studies to include LpxC enzymes from Gram-negative pathogens Y. pestis (bubonic plague) and F. tularensis (tularemia) [Cole et al. (2011) Biochemistry 50, 258.]

 

Figure 3: Structure and biological function of LpxC. This zinc enzyme catalyzes the first committed step of lipid A biosynthesis; lipid A is the hydrophobic anchor of lipopolysaccharide, which comprises the outer leaflet of the outer membrane of Gram-negative bacteria. The crystal structure of LpxC reveals a hydrophobic tunnel in the active site that accommodates the fatty acid moiety of the substrate, and this binding interaction is required for the active site to adopt a catalytically-active conformation.

 

Structural Basis of Terpenoid Biosynthesis

 

The family of terpenoid natural products currently numbers more than 70,000 members found in all forms of life. Terpenoids, are involved in diverse biological functions such as the mediation of plant-parasite interactions or the modulation of membrane fluidity. Since times of antiquity, terpenoid natural products have also been essential components of the pharmacopeia as analgesics, antibiotics, and anti-cancer compounds (e.g., Taxol). We are interested in the enzymes that catalyze the biosynthesis of different cyclic terpenoids [Christianson (2006) Chem. Rev. 106, 3412; Christianson (2008) Curr. Opin. Chem. Biol. 12, 141]. We have determined the three-dimensional crystal structures of terpenoid cyclases from various bacterial, fungal, and plant sources, such as epi-isozizaene synthase from S. colicolor [Aaron et al. (2010) Biochemistry 49, 1787], bornyl diphosphate synthase from culinary sage [Whittington et al. (2002), Proc. Natl. Acad. Sci. USA 99, 15375], aristolochene synthase from A. terreus [Shishova et al. (2007) Biochemistry 46, 1941], trichodiene synthase from F. sporotrichioides [Rynkiewicz et al. (2001) Proc. Natl. Acad. Sci. USA 98, 13543], δ-cadinene synthase from cotton [Gennadios et al. (2009) Biochemistry 48, 6175] and taxadiene synthase from the Pacific yew (which catalyzes the first committed step in the biosynthesis of Taxol, a potent cancer chemotherapeutic compound), [Köksal et al. (2011) Nature 469, 116]. To illustrate, structures of bornyl diphosphate synthase and taxadiene synthase are shown in Figures 4 and 5, respectively. These structures guide the study of site-specific mutants and alternative substrates as we explore the structural basis of diversity in terpenoid biosynthesis [e.g., see: Vedula et al. (2005) Biochemistry 44, 12719; Vedula et al. (2008) Arch. Biochem. Biophys. 469, 184; Christianson (2007) Science 316, 60], Köksal et al. (2012) Biochemistry 51, 3003, 301.

 

Figure 4: Reaction catalyzed by bornyl diphosphate synthase. Aza analogues of carbocation intermediates are shown in boxes; crystal structures of their complexes with the synthase reveal structural inferences on catalysis. The enzyme undergoes significant conformational changes upon the binding of 3 Mg2+ ions and pyrophosphate (or a substrate diphosphate group). These conformational changes sequester the active site from bulk solvent and trigger substrate ionization to initiate catalysis [Whittington et al. (2002) Proc. Natl. Acad. Sci. USA 99, 15375].

Figure 5: Structural relationships among terpenoid cyclases.The class I terpenoid cyclase fold of pentalenene synthase (blue) contains metal-binding motifs DDXXD and (N,D)DXX(S,T)XXXE (red and orange, respectively); in 5-epi-aristolochene synthase, this domain is linked to a smaller, vestigial domain (green). A related domain is found in the class II terpenoid cyclase fold of squalene-hopene cyclase, where it contains the general acid motif DXDD (brown) and a second domain (yellow) inserted between the first and second helices; a hydrophobic plateau flanking helix 8 (gray stripes) enables membrane insertion. Taxadiene synthase contains both class I and class II terpenoid cyclase folds, but only the class I domain is catalytically active. The role of N-termini (purple) in class I plant cyclases is to "cap" the active site, as shown for 5-epi-aristolochene synthase.

Selected Publications: 

Köksal, M., Jin, Y., Coates, R.M., Croteau, R., Christianson, D.W. (2011) Taxadiene Synthase Structure and Evolution of Modular Architecture in Terpene Biosynthesis. Nature 469, 116-120. 

 

Cole, K.E., Gattis, S.G., Angell, H.D., Fierke, C.A., Christianson, D.W. (2011) Structure of the Metal-Dependent Deacetylase LpxC from Yersinia enterocolitica Complexed with the Potent Inhibitor CHIR-090. Biochemistry 50, 258-265.

 

Lombardi, P.M., Angell, H.D., Whittington, D.A., Flynn, E.F., Rajashankar, K.R., Christianson, D.W. (2011) Structure of Prokaryotic Polyamine Deacetylase Reveals Evolutionary Functional Relationships with Eukaryotic Histone Deacetylases. Biochemistry 50, 1808-1817.

 

Köksal, M., Hu, H., Coates, R.M., Peters, R.J., Christianson, D.W. (2011) Structure and Mechanism of the Diterpene Cyclase ent-Copalyl Diphosphate Synthase. Nature Chem. Biol. 7, 431-433.

 

Cole, K.E., Dowling, D.P., Boone, M.A., Phillips, A.J., Christianson, D.W. (2011) Structural Basis of the Antiproliferative Activity of Largazole, a Depsipeptide Inhibitor of the Histone Deacetylases. J. Am. Chem. Soc. 133, 12474-12477 (Communication to the Editor).

 

Ilies, M., Di Costanzo, L., Dowling, D.P., Thorn, K.J., Christianson, D.W. (2011) Binding of α, α-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design. J. Med. Chem. 54, 5432-5443.

 

Lombardi, P.M., Cole, K.A., Dowling, D.P., Christianson, D.W. (2011) Structure, Mechanism, and Inhibition of Histone Deacetylases and Related Metalloenzymes. Curr. Op. Struct. Biol. 21, 735-743 (invited review). 

 

Köksal, M., Chou, W.K.W., Cane, D.E., Christianson, D.W. (2012) Structure of 2-Methylisoborneol Synthase from Streptomyces coelicolor and Implications for the Cyclization of a Noncanonical C-Methylated Monoterpenoid Substrate. Biochemistry 51, 3011-3020.

 

Deardorff, M.A., Bando, M., Nakato, R., Watrin, E., Itoh, T., Minamino, M., Saitoh, K., Komata, M., Katou, Y., Clark, D., Cole, K.E., De Baere, E., Decroos, C., Di Donato, N., Ernst, S., Francey, L.J., Gyftodimou, Y., Hirashima, K., Hullings, M., Ishikawa, Y., Jaulin, C., Kaur, M., Kiyono, T., Lombardi, P.M., Magnaghi-Jaulin, L., Mortier, G.R., Nozaki, N., Petersen, M.B., Seimiya, H., Siu, V.M., Suzuki, Y., Takagaki, K., Wilde, J.J., Willems, P.J., Prigent, C., Gillessen-Kaesbach, G., Christianson, D.W., Kaiser, F.J., Jackson, L.G., Hirota, T., Krantz, I.D., Shirahige, K. (2012) HDAC8 Mutations in Cornelia de Lange Syndrome Affect the Cohesin Acetylation Cycle. Nature 489, 313-317.

 

D'Antonio, E.L., Hai, Y., Christianson, D.W. (2012) Structure and Function of Non-Native Metal Clusters in Human Arginase I. Biochemistry 51, 8399-8409.

 

D'Antonio, E.L., Ullman, B., Roberts, S.C., Gaur Dixit, U., Wilson, M.E., Hai, Y., Christianson, D.W. (2013) Crystal Structure of Arginase from Leishmania mexicana and Implications for the Inhibition of Polyamine Biosynthesis in Parasitic Infections. Arch. Biochem. Biophys. 535, 163-176.

 

Genshaft, A., Moser, J.-A.S., D'Antonio, E.L., Bowman, C.M., Christianson, D.W. (2013) Energetically Unfavorable Amide Conformations for N6-Acetyllysine Side Chains in Refined Protein Structures. Proteins: Struct., Funct., Bioinf. 81, 1051–1057

 

Köksal, M., Chou, W.K.W., Cane, D.E., Christianson, D.W. (2013) Unexpected Reactivity of 2-Fluorolinalyl Diphosphate in the Active Site of Crystalline 2-Methylisoborneol Synthase. Biochemistry 52, 5247-5255.

 

Chen, M., Al-lami, N., Janvier, M., D'Antonio, E.L., Faraldos, J.A., Cane, D.E., Allemann, R.K., Christianson, D.W. (2013) Mechanistic Insights from the Binding of Substrate and Carbocation Intermediate Analogues to Aristolochene Synthase. Biochemistry 52, 5441-5453.

 

Hai, Y., Dugery, R.J., Healy, D., Christianson, D.W. (2013) Formiminoglutamase from Trypanosoma cruzi is an Arginase-Like Manganese Metalloenzyme. Biochemistry 52, 9294-9309.

 

Li, R., Chou, W.K.W., Himmelberger, J.A., Litwin, K.M., Harris, G.G., Cane, D.E., Christianson, D.W. (2014) Reprogramming the Chemodiversity of Terpenoid Cyclization by Remolding the Active Site Contour of epi-Isozizaene Synthase. Biochemistry 53, 1155-1168.

 

Kaiser, F.J., Ansari, M., Braunholz, D., Gil-Rodríguez, M.C., Decroos, C., Wilde, J.J., Fincher, C.T., Kaur, M., Bando, M., Bowman, C.M., Bradley, J., Clark, D., del Campo-Casanelles, M., Di Donato, N., Dubbs, H., Eckhold, J., Ernst, S., Ferreira, J.C., Francey, L., Gehlken, U., Guillén-Navarro, E., Gyftodimou, Y., Hall, B.D., Hennekam, R., Hullings, M., Hunter, J., Kline, A.D., Krumina, Z., Leppig, K., Lynch, S.A., Mallozzi, M.B., Mannini, L., McKee, S., Mehta, S., Micule, L., Mohammed, S., Moran, E., Mortier, G.R., Moser, J.-A.S., Nozaki, N., Nunes, L., Pappas, J., Pérez-Aytés, A., Petersen, M.B., Poffyn, A., Puisac, B., Revencu, N., Roeder, E., Saitta, S., Scheuerle, A., Siu, V.M., Thiese, H., Vater, I., Willems, P., Williamson, K., Wilson, L., Hakonarson, H., Wierzba, J., Musio, A., Gillessen-Kaesbach, G., Ramos, F.J., Jackson, L.G., Shirahige, K., Pié, J., Christianson, D.W., Krantz, I.D., FitzPatrick, D.R., Deardorff, M.A. (2014) HDAC8 Mutations Cause an X-Linked Clinically Recognizable Cornelia de Lange Syndrome-Like Disorder. Hum. Mol. Genet. 23, 2888-2900 (cover article).

 

Hai, Y., Edwards, J.E., Van Zandt, M.C., Hoffmann, K.F., Christianson, D.W. (2014) Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis. Biochemistry 53, 4671-4684.

 

Decroos, C., Bowman, C.M., Moser, J.-A.S., Christianson, K.E., Deardorff, M.A., Christianson, D.W. (2014) Compromised Structure and Function of HDAC8 Mutants in Cornelia de Lange Syndrome Spectrum Disorders. ACS Chem. Biol. 9, 2157-2164.

 

Hai, Y., Kerkhoven, E.J., Barrett, M.P., Christianson, D.W. (2015) Crystal Structure of an Arginase-Like Protein from Trypanosoma brucei that Evolved without a Binuclear Manganese Cluster. Biochemistry 54, 458-471.

 

Decroos, C., Clausen, D.J., Haines, B.E., Wiest, O., Williams, R.M., Christianson, D.W. (2015) Variable Active Site Loop Conformations Accommodate the Binding of Macrocyclic Largazole Analogues to HDAC8. Biochemistry 54, 2126-2135.

David M. Chenoweth

Photo: 
First Name: 
David M.
Last Name: 
Chenoweth
Official Title: 
Associate Professor of Chemistry

Organic and Bioorganic Chemistry

Contact Information
Office Location: 
2002 IAST, lab: 2020,2080,2100 IAST
Email: 
dcheno@sas.upenn.edu
Phone: 
215-­573-­1953
Admin Support: 
Education: 
  • B.S. Indiana University-Purdue University Indianapolis (1999)
  • Organic Chemist, Eli Lilly & Co., Indianapolis, IN (2000 – 2004)
  • Ph.D. California Institute of Technology (2009)
  • Kanel Foundation Predoctoral Fellow (2007 – 2009)
  • Caltech Herbert Newby McCoy Award (2009)
  • NIH/NIGMS Postdoctoral Fellow, Massachusetts Institute of Technology (2009 – 2010)
Research Interests: 

Research in the Chenoweth laboratory is grounded in organic chemistry and molecular recognition with applications to biological and materials problems. We synthesize molecules and study their properties and interactions for a broad range of applications in bioorganic and materials chemistry. We are particularly interested in the design and synthesis of new molecules that can modulate nucleic acid and protein structure. Additionally, we are equally interested in the synthesis of new materials with sensing and self-assembly properties.

 

Undergraduate students, graduate students, and postdoctoral researchers are exposed to a diverse array of topics including organic chemistry, synthesis, bioorganic chemistry, macromolecular structure (nucleic acids and proteins), biochemistry, and polymer chemistry.

Selected Publications: 

Zhang, Yitao; Malamakal, Roy M.; Chenoweth, David M. “Aza-Glycine Induces Collagen Hyperstability” J. Am. Chem. Soc. 2015, ASAP. DOI: 10.1021/jacs.5b04590. See Chemical & Engineering News story by Stu Borman: “Chemical Modification Is Best Ever At Strengthening And Stabilizing Collagen” Chemical & Engineering News, Volume 93, Issue 38, p. 7, News of The Week.

 

Zhang, Yitao; Malamakal, Roy M.; Chenoweth, David M. “A Single Stereodynamic Center Modulates the Rate of Self-Assembly in a Biomolecular System” Angew. Chem. Int. Ed. 2015, 54, 10826-10832.

 

Suh, Sung-Eun; Barros, Stephanie A.; Chenoweth, David M. “Triple Aryne–Tetrazine Reaction Enabling Rapid Access to a New Class of Polyaromatic Heterocycles” Chemical Science 2015, 6, 5128-5132.

 

Tran, Mai N.; Chenoweth, David M. “Synthesis and Properties of Lysosome-Specific Photoactivatable Probes for Live-Cell Imaging” Chemical Science 2015, 6, 4508-4512.

 

Barros, Stephanie A.; Chenoweth, David M. “Triptycene-Based Small Molecules Modulate (CAG)·(CTG) Repeat Junctions" Chemical Science 2015, 6, 4752-4755.

 

Tran, Mai N.; Chenoweth, David M. “Photoelectrocyclization as an Activation Mechanism for Organelle Specific Live-Cell Imaging Probes” Angew. Chem. Int. Ed. 2015, 54, 6442-6446.

 

Ballister, Edward R.; Ayloo, Swathi; Chenoweth, David M.; Lampson, Michael A.; Holzbaur, Erika L.F. “Optogenetic Control of Organelle Transport Using a Photocaged Chemical Inducer of Dimerization” Current Biology 2015, 10, R407-R408.

 

Ballister, Edward R.; Aonbangkhen, Chanat; Mayo, Alyssa M.; Lampson, Michael A.; Chenoweth, David M. "Localized Light-Induced Protein Dimerization in Living Cells using a Photocaged Dimerizer” Nature Communications 2014, 5, 5475.

 

Barros, Stephanie A.; Chenoweth, David M. "Recognition of Nucleic Acid Junctions Using Triptycene-Based Molecules” Angew. Chem. Int. Ed. 2014, 53, 13746-13750.

 

Rarig, Robert-André F.; Tran, Mai N.; Chenoweth, David M. "Synthesis and Conformational Dynamics of the Reported Structure of Xylopyridine A” J. Am. Chem. Soc. 2013, 135, 9213–9219, ASAP.

 

Chenoweth, David M.; Meier, Jordan L.; Dervan, Peter B. "Pyrrole-Imidazole Polyamides Distinguish Between Double-Helical DNA and RNA” Angew. Chem. Int. Ed. 2013, 52, 415-418.

 

Weizmann, Yossi; Chenoweth, David M.; Swager, Timothy, M. "DNA−CNT Nanowire Networks for DNA Detection” J. Am. Chem. Soc. 2011, 133, 3238–3241.

 

Chenoweth, David M.; Dervan, Peter B. “Structural Basis for Cyclic Py-Im Polyamide Allosteric Inhibition of Nuclear Receptor Binding” J. Am. Chem. Soc. 2010, 132, 14521. Selected for the cover of JACS Oct. 20, 2010, Vol 132, Issue 41. Covered by Chemical and Engineering News Sept. 27, 2010 issue, “Putting DNA in a Bind”.

 

Weizmann, Yossi; Chenoweth, David M.; Swager, Timothy, M. “Addressable Terminally-Linked DNA-CNT Nanowires” J. Am. Chem. Soc. 2010, 132, 14009.

 

Weizmann, Yossi; Lim, Jeewoo; Chenoweth, David M.; Swager, Timothy, M. “Regiospecific Synthesis of Au-Nanorod/SWCNT/Au-Nanorod Heterojunctions” Nano Lett. 2010, 10, 2466.

 

Chenoweth, Kimberly; Chenoweth, David M.; Goddard III, William A. “Cyclooctyne-based Reagents for Uncatalyzed Click Chemistry: A Computational Survey” Org. Biomol. Chem. 2009, 7, 5255.

 

Chenoweth, David M.; Harki, Daniel A.; Dervan, Peter B. “Oligomerization Route to DNA Binding Py-Im Polyamide Macrocycles” Org. Lett. 2009, 11, 3590.

 

Chenoweth, David M.; Dervan, Peter B. “Allosteric Modulation of DNA by Small Molecules” Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 13175. Covered by Nature News: "Get into the groove" Nature 2009, 460, 669. Also selected by the Stanford Synchrotron (SSRL) as a science highlight for November 2009.

 

Chenoweth, David M.; Harki, Daniel A.; Dervan, Peter B. “Solution-Phase Synthesis of Pyrrole-Imidazole Polyamides” J. Am. Chem. Soc. 2009, 131, 7175.

 

Chenoweth, David M.; Harki, Daniel A.; Phillips, John W.; Dose, Christian; Dervan, Peter B. “Cyclic Pyrrole-Imidazole Polyamides Targeted to the Androgen Response Element” J. Am. Chem. Soc. 2009, 131, 7182.

 

Chenoweth, David M.; Chenoweth, Kimberly; Goddard III, William A. “Lancifodilactone G: Insights about an Unusually Stable Enol” J. Org. Chem., 2008, 73, 6853.

 

Dose, Christian; Farkas, Michelle E.; Chenoweth, David M.; Dervan, Peter B. “Next Generation Hairpin Polyamides with (R)-3,4-Diaminobutyric Acid Turn Unit” J. Am. Chem. Soc., 2008, 130, 6859.

 

Chenoweth, David M.; Viger, Anne; Dervan, Peter B. “Fluorescent Sequence-Specific dsDNA Binding Oligomers” J. Am. Chem. Soc., 2007, 129, 2216. Covered by Chemical and Engineering News.

 

Chenoweth, David M.; Poposki, Julie A.; Marques, Michael A.; Dervan, Peter B. “Programmable oligomers targeting 5'-GGGG-3' in the minor groove of DNA and NF-k B binding inhibition” Bioorg. Med. Chem., 2007, 15, 759.

 

Doss, Raymond M.; Marques, Michael M.; Foister, Shane; Chenoweth, David M.; Dervan, Peter B. “Programmable Oligomers for Minor Groove DNA Recognition” J. Am. Chem. Soc., 2006, 128, 9074.

 

Nurok, D.; Frost, M. C.; Chenoweth, D. M. “Separation using planar chromatography with electroosmotic flow” J. Chromatogr., A, 2000, 903, 211. 

 

Nurok, David; Frost, Megan C.; Pritchard, Cary L.; Chenoweth, David M. “The performance of planar chromatography using electroosmotic flow” J. Planar Chromatogr.-Mod. TLC, 1998, 11, 244.

J. Kent Blasie

Photo: 
First Name: 
J. Kent
Last Name: 
Blasie
Official Title: 
Walter H. & Leonore C. Annenberg Professor in the Natural Sciences

Biological, Chemical Physics and Physical Chemistry

Contact Information
Office Location: 
2003 Vagelos, Lab: Vagelos 2170, 2190, 2210-2211, 2230-2231 and 2240
Email: 
jkblasie@sas.upenn.edu
Phone: 
(215) 898-6208
Education: 
  • B.S. University of Michigan (1964)
  • Ph.D. University of Michigan (1968)
  • USPHS Career Development Award (1971-76)
  • Guest Biophysicist, Brookhaven National Laboratory (1973-present)
  • Chairman, Department of Chemistry (1983-1986)
  • Director, Biostructures Participating Research Team, National Synchrotron Light Source, Brookhaven National Laboratory (1985-1994)
  • Executive Committee, Complex Materials Collaborative Access Team, Advanced Photon Source, Argonne National Laboratory (1994-present)
  • Scientific Advisory Committee & Advisory Board, Spallation Neutron Source, Oak Ridge National Laboratory (1997-2006)
  • Executive Committee, Cold Neutrons in Biology and Technology Team, National Institutes of Standards and Technology (1998-2006)
  • Director, Complex Materials Collaborative Access Team, Advanced Photon Source, Argonne National Laboratory (2001-present)
Research Interests: 

Our research program falls into two areas, namely nano-scale materials science and fundamental biophysics (or biophysical chemistry). The materials science effort is directed toward the development of novel electro-optical devices, both single particle and 2-D to 3-D ensemble based, utilizing the unique microscopic properties of designed cofactor-artificial peptide complexes. The cofactors are based primarily on extended conjugated chromophores designed to exhibit light-induced electric charge transfer over large nano-scale distances and possess minimal HOMO-LUMO bandgaps. The highly stable, artificial α-helical peptides are based on n-helix bundle structural motifs designed to vectorially incorporate the cofactor within the core of the bundle and to order the assembly of the peptide-cofactor complexes at the liquid-gas, solid-liquid or solid-gas interface. Ensembles of these complexes have potential for both photovoltaic devices applications relevant to solar energy conversion and non-linear optical device applications relevant to broad-band communications. The structures and properties of both the isolated complexes and the ensembles thereof are determined by cutting-edge techniques, including molecular dynamics simulation, synchrotron x-ray and cold neutron scattering, and polarized CW and transient spectroscopies. The biophysics effort is directed toward understanding the mechanism of volatile general anesthetic action on membrane ion channels. To better access the physical chemistry of the anesthetic-protein interaction, we are utilizing artificial membrane ion channels based on an amphiphilic 4-helix bundle motif, the hydrophilic domain designed to possess the anesthetic binding cavity and the hydrophobic domain designed as a membrane-spanning cation channel. The same techniques mentioned above are utilized to probe the nature of the anesthetic-peptide interaction and its effect on the conformation of the ion channel domain. Future work will also be directed toward understanding the mechanism of electro-mechanical coupling in the substantially more complex, natural voltage-gated ion channels under the control of the applied transmembrane electrochemical potential. These studies will employ cutting-edge time-resolved synchrotron x-ray and cold neutron scattering techniques coupled with molecular dynamics simulation, and will lead to the investigation of the effects of anesthetic binding on this mechanism. All of the work mentioned above involves both extensive collaborations with other faculty in the Department, at Penn, and elsewhere, as well as experimental work at the National Laboratories on a regular basis.

Figure Legend #1: An instantaneous configuration from a molecular dynamics simulation of the structure of an extended conjugated chromophore (a butadiyne-bridged Zn-porphyrin dimer: red/yellow) incorporated into the core of the hydrophilic domain of an amphiphilic 4-helix bundle peptide (green ribbon representation) and vectorially-oriented at the water-octane (gray-pink) interface. The time-averaged structure of the chromophore-peptide complex within a monolayer ensemble at the interface has been determined experimentally. The designed coiled-coil structure of the 4-helix bundle induces a twist in the chromophore that is key to optimizing its non-linear optical polarizability.

Figure Legend #2: Instantaneous configurations from molecular dynamics simulations of the structures of a computationally designed, model anesthetic-binding membrane ion channel vectorially-oriented at the water-octane interface (water/octane not shown; see Figure 1). The hydrophilic domain (blue ribbon representation) of the amphiphilic 4-helix bundle peptide contains the anesthetic-binding cavity with the volatile anesthetic halothane (CPK representation) in the cavity shown on the right-side, with the ion channel hydrophobic domain (red ribbon representation). The helices are relatively straight and un-coiled in the side-on view (upper), as more readily seen in the end-on view shown below. Removal of the anesthetic from the cavity is seen to induce a coiled-coil structure extending from the cavity into the ion channel hydrophobic domain, shown in the side-on and end-on views on the left side. Importantly, this anesthetic-dependent conformational change depends upon the amino acid composition of the cavity. Experimental verification of these predictions from the computational design and molecular dynamics simulations are underway.

Selected Publications: 

 

Gupta, S., Dura, J., Freites, A. Tobias, D. and Blasie, J.K. Structural characterization of the voltage sensor domain and voltage-gated K+-channel vectorially-oriented within a single bilayer membrane at the solid/vapor and solid/liquid interfaces via neutron interferometry. Submitted.

 

Koo, J., Park, J., Tronin, A., Zhang, R., Krishnan, V., Strzalka, J., Kuzmenko, I., Therien, M.J. and Blasie, J.K. Acentric 2-D Ensembles of D-br-A Electron-Transfer Chromophores via Vectorial Orientation within Amphiphilic n-Helix Bundle Peptides for Photovoltaic Device Applications. Langmuir, 28: (6), pp 3227-3238

http://pubs.acs.org/doi 

 

Gupta, S., Liu, J., Strzalka, J. and Blasie, J.K. (2011) Profile Structures of the VSD and KvAP Channel Vectorially-Oriented in Single Membranes at Solid-Vapor or Solid-Liquid Interfaces via X-ray Reflectivity. Phys. Rev. E. 84(3): 031911-1-15. 

http://pre.aps.org/

 

Korendovych, I., Senes, A., Kim, Y.H., Lear, J., Fry, H.C., Therien, M.J., Blasie, J.K., Walker, F.A. and DeGrado, W.F. (2010) De Novo Design and Molecular Assembly of a Transmembrane Diporphyrin-Binding Protein Complex. J. Am. Chem. Soc. Comm. 132: 15516-15518. 

http://pubs.acs.org/Volume=132

 

Gonella, G., Dai, H.-L., Fry, H. C., Therien, M. J., Krishnan, V., Tronin, A. and Blasie, J.K. (2010) Control of the Orientational Order and Nonlinear Optical Response of the "Push-Pull" Chromophore RuPZn via Specific Incorporation into Densely-Packed Monolayer Ensembles of an Amphiphilic 4-Helix Bundle Peptide: Second Harmonic Generation at High Chromophore Densities. J. Am. Chem. Soc. 132 (28): 9693–9700. 

http://pubs.acs.org/Volume=132 (28) 

 

Krishnan, V., Tronin, A., Strzalka, J., Fry, H.C., Therien, M.J. and Blasie, J.K. (2010) Control of the Orientational Order and Nonlinear Optical Response of the “Push-Pull” Chromophore RuPZn via Specific Incorporation into Densely-Packed Monolayer Ensembles of an Amphiphilic 4-Helix Bundle Peptide: Characterization of the Cofactor-Peptide Complex in Monolayer Ensembles. J. Am. Chem. Soc. 132(32):11083-11092. 

http://pubs.acs.org/Volume=132 (32) 

 

Krishnan, V., Strzalka, J., Liu, J., Liu, C., Kuzmenko, I., Gog, T. and Blasie, J.K. (2010) Interferometric Enhancement of X-ray Reflectivity from Unperturbed Langmuir Monolayers of Amphiphiles at the Liquid-Gas Interface. Phys. Rev. E 81: 021604-1-10. 

http://pre.aps.org/abstract 

 

Zou, H. Liu, J. and Blasie, J.K. (2009) Mechanism of interaction between the volatile anesthetic halothane and a model ion channel protein: III. Molecular dynamics simulation incorporating a cyano-phenylalanine spectroscopic probe. Biophys. J. 96(10) pp. 4188 – 4199.

http://biophysj/Volume96=16

 

Liu, J., Strzalka, J., Tronin, A., Johansson, J.S. and Blasie, J.K. (2009) Mechanism of interaction between the volatile anesthetic halothane and a model ion channel protein: II. Fluorescence & vibrational spectroscopy employing a cyano-phenylalanine probe. Biophys. J. 96(10) pp. 4176 – 4187.

http://biophysj/Volume96

 

Strzalka, J., Liu, J., Tronin, A., Johansson, J.S. and Blasie, J.K. (2009) Mechanism of interaction between the volatile anesthetic halothane and a model ion channel protein: I. Structural investigations via x-ray reflectivity from Langmuir monolayers. Biophys. J. 96(10) pp. 4164 – 4175.

http://biophysj/Volume96

 

Tronin, A., Krishnan, V., Strzalka, J., Kuzmenko, I., Gog, T., Fry, C., Therien, M.J. and Blasie, J.K. (2009) Portable UV-VIS spectrometer for measuring absorbance and dichroism of Langmuir monolayers. Rev. Sci. Instru. 80(3): 033102-1-7.

http://rsi.aip.org/

 

Zou, H., Therein, M.J. and Blasie, J.K. Structure & Dynamics of an Extended Conjugated NLO Chromophore within an Amphiphilic 4-Helix Bundle Peptide by Molecular Dynamics Simulation. Submitted to J. Phys. Chem. B.

 

McAllister, K.A., Zou, H., Cockran, F.V., Bender, G.M., Senes, A., Fry, C.F., Nanda, V., Keenan, P.A., Lear, J.D., Therien, M.J., Blasie, J.K, and DeGrado, W.F. Using α-Helical Coiled-Coils to Design Nanostructured Metalloporphyrin Arrays. Submitted to Angewandte Chemie.

 

Bender, G.M., Lehmann, A., Zou, H., Cheng, H., Fry, H.C., Engel, D., Therien, M.J., Blasie, J.K., Roder, H., Saven, J.G. and DeGrado, W.F. De Novo Design of a Single Chain Diphenylporphyrin Metalloprotein. J. Am. Chem. Soc. 129(35). 

http://pubs.acs.org/Volume=129

 

Zou, H., Strzalka, J. Xu, T., Tronin, A. and Blasie, J.K. (2007) 3-D Structure and Dynamics via Molecular Dynamics Simulation of a de novo Designed, Amphiphilic Heme Protein Maquette at Soft Interfaces. Phys. Chem. B 111: 1823-1833.

http://pubs.acs.org

 

Strzalka, J., Xu, T., Tronin, A., Wu, S.P., Miloradovic, I., Kuzmenko, I. Gog, T., Therien, M.J., and Blasie, J.K. (2006) Structural Studies of Amphiphilic 4-helix Bundle Peptides Incorporating Designed Extended Chromophores for Nonlinear Optical Biomolecular Materials. Nano Lett. 6(11): 2395-2405. 

http://pubs.acs.org/Volume=6

 

Xu, T., Wu, S.P., Miloradovic, I., Therien, M.J., and Blasie, J.K. (2006) Incorporation of Designed Extended Chromophores into Amphiphilic 4-helix Bundle Peptides for Nonlinear Optical Biomolecular Materials. Nano Lett. 6(11): 

http://pubs.acs.org/Volume=6(2387-2394)

 

Nordgren, C.E., Strzalka, J.W. and Blasie, J.K (2005) Structure of α-Helical Bundle Peptides Vectorially-Oriented at Soft Interfaces via Molecular Dynamics Simulations and X-ray/Neutron Scattering. Submitted to Langmuir.

 

Churbanova, I., Tronin, A., Strzalka, J.W., Gog, T., Kuzmenko, I., Johansson, J.S. and Blasie, J.K. (2006) Monolayers of a Model Anesthetic-Binding Membrane Protein: Formation, Characterization and Halothane-Binding Affinity. Biophys. J. 90: 3255-3266. 

http://www.cell.com/biophysj/Volume=90

 

Tronin, A., Xu, T. and Blasie, J.K. (2005) In situ Determination of Orientational Distributions in Langmuir Monolayers by Total Internal Reflection Fluorescence. Langmuir 21: 7760-7767.

http://dx.doi.org/

 

 

Discher, B.M., Noy, D., Strazalka, J, Ye, S., Moser, C.C., Lear, J.D., Blasie, J.K. and Dutton, P.L. (2005) Design of Amphiphilic Protein Maquettes: Controlling Assembly, Membrane Insertion, and Cofactor Interactions. Biochemistry 44:12329-12343.

http://pubs.acs.org/Volume=44

 

Ye, S., Discher, B.M., Strzalka, J.W., Xu, T., Wu, S.P., Noy, D., Kuzmenko, I., Gog, T., Therien, M.J., Dutton, P.L. and Blasie, J.K. (2005) Amphiphilic 4-Helix Bundles Designed for Light-Induced Electron Transfer Across Soft Interfaces. Nano Lett. 5(9):1658-1667.

http://dx.doi.org/

 

Ye, S., Strzalka, J., Churbanova, I.Y., Zheng, S,, Johansson, J.S. and Blasie JK. (2004) A Model Membrane Protein for Binding Volatile Anesthetics. Biophys. J. 87: 4065-4074.

http://www.cell.com/biophysj/Volume=87

 

Strzalka, J. DiMasi, E., Kuzmenko, I., Gog, T. and Blasie, J.K. (2004) Resonant X-ray Reflectivity from a Bromine-Labeled Fatty-Acid Langmuir Monolayer. Phys. Rev. E 70: 051603-1-5. 

http://pre.aps.org/abstract/PRE/v70/i5/e051603

 

Strzalka, J., Kneller, L.R., Gibney, B.R., Satija, S., Majkrzak, C.F. and Blasie, J.K. (2004) Specular Neutron Reflectivity and Structure of Artificial Protein Maquettes Vectorially Oriented at Interfaces. Phys. Rev. E. E 70: 061905-1-10. 

http://pre.aps.org/abstract/PRE/v70/i6/e061905 

 

Ye, S., Discher, B.M., Strzalka, J.W., Noy, D., Zheng, S., Dutton, P.L. and Blasie, J.K. (2004) Amphiphilic 4-Helix Bundles Designed for BioMolecular Materials Applications. Langmuir 20(14): 5897-5904.

http://dx.doi.org/

 

Blasie, J.K., Strzalka, J. and Zheng, S. (2003) Solution to the Phase Problem for Specular X-ray & Neutron Reflectivity from Thin Films on Liquid Surfaces. Phys. Rev. B 67: 224201-1--224201-8.

http://prb.aps.org/

 

Ye, S., Strzalka, J., Chen, X., Moser, C.C., Dutton, P.L. and Blasie, J.K. (2003) Assembly of a Vectorially-Oriented Four-Helix Bundle at the Air/Water Interface via Directed Electrostatic Interactions. Langmuir 19(5): 1515-1521.

http://pubs.acs.org/Vol=19

 

 

Zheng, S., Strzalka, J., Jones, D.H., Opella, S.J. and Blasie, J.K. (2003) Comparative Structural Studies of Vpu Peptides in Phospholipid Monolayers by X-ray Scattering. Biophys. J. 84(4): 2393-2415.

http://www.cell.com/Vol 84 

 

Lopez, C. F., Montal, M., Blasie, J.K., Klein, M.L. and Moore, P.B. (2002) Molecular Dynamics Investigation of Membrane-Bound Bundles of the Channel Forming Transmembrane Domain of Viral Protein U from the Human Immunodeficiency Virus HIV. Biophys. J. 83(3): 1259-1267.

http://biophysj/ Volume83

 

Nordgren, E., Tobias, D.J., Klein, M.L. and Blasie, J.K. (2002) Molecular Dynamics Simulations of a Hydrated Protein Vectorially-Oriented at Hydrophobic vs. Hydrophilic Soft Surfaces. Biophys. J. 83(6): 2906-2917.

http://www.cell.com/biophysj/Volume=83

 

Tronin, A., Edwards, A.M., Wright, W.W., Vanderkooi, J.M. and Blasie, J.K. (2002) Orientational Distributions for Cytochrome c on Polar & Nonpolar Soft Surfaces by Polarized Total Internal Reflection Fluorescence. Biophys. J. 82: 996-1003.

http://www.cell.com/biophysj/Volume=82

 

Haas, A.S., Pilloud, D.L., Reddy, K.S., Babcock, G.T., Moser, C.C., Blasie, J.K. and Dutton, P.L. Cytochrome c and Cytochrome c Oxidase: Monolayer Assemblies and Catalysis. (2001) J. Phys. Chem. B 105(45): 11351-11362. 

http://pubs.acs.org/Volume=105

 

 

 

Tronin, A. and Blasie, J.K. Variable Acquisition Angle Total Internal Reflection Fluorescence – a New Technique for Orientation Distribution Studies of Ultrathin Films. (2001) Langmuir 17(No. 12): 3696-3703.

http://pubs.acs.org/Volume=17

 

Tronin, A., Strzalka, J., Chen, X., Dutton, P.L., Ocko, B.M. and Blasie, J.K. (2001) Orientational Distributions of the Di-α-Helical Synthetic Peptide ZnPPIX-BBC16 by X-ray Reflectivity and Polarized Epifluorescence. Langmuir 17(10): 3061-3066.

http://pubs.acs.org/Volume=17

 

Zheng, S., Strzalka, J., Ma, C., Opella, S.J., Ocko, B.M. and Blasie, J.K. (2001) Structural Studies of the HIV-1 Accessory Protein Vpu in Langmuir Monolayers: Synchrotron X-ray Reflectivity. Biophys. J. 80(4): 1837-1850.

http://www.cell.com/biophysj/Vol80

 

Kneller, L.R. , Edwards, A.M., Majkrzak, C.F., Berk, N.F., Krueger, S. and Blasie, J.K. (2001) Hydration State of a Single Cytochrome c Monolayer Vectorially-Oriented at a Soft Interface Investigated via Neutron Interferometry. Biophys. J. 80(5): 2248-2261.

http://www.cell.com/biophysj/s?searchTerms=&searchAuthor=&searchVol80 

 

Strzalka, J., Chen, X., Dutton, P.L. and Blasie, J.K. (2001) X-ray Scattering Studies of Maquette Peptide Monolayers II: Interferometry at the Solid/Vapor Interface. Langmuir 17(4): 1193-1199.

http://pubs.acs.org/Volume=17

 

Tronin, A., Strzalka, J., Chen, X., Dutton, P.L. and Blasie, J.K. (2000) Determination of the Porphyrin Orientation Distribution in Langmuir Monolayers by Polarized Epifluorescence. Langmuir 16(25): 9878-9886.

http://pubs.acs.org/Volume=16

 

Strzalka, J., Chen, X., Dutton, P.L., Ocko, B. M. and Blasie, J.K. (2000) X-ray Scattering Studies of Maquette Peptide Monolayers I: Reflectivity and GID at the Air/Water Interface. Langmuir 16(26): 10404-10418.

http://pubs.acs.org/Volume=16

 

A.M. Edwards, K. Zhang, C.E. Nordgren and J.K. Blasie. (2000) Heme Structure & Orientation in Single Monolayers of Cytochrome c on Polar & Nonpolar Soft Surfaces. Biophys. J. 79: 3105-3117.

http://www.cell.com/biophysj/Vol 79

 

Blasie, J.K. and Timmins, P. (1999) Neutron Scattering in Structural Biology & BioMolecular Materials in Neutron Scattering in Materials Research, eds. T. Mason and A. Taylor, MRS Bulletin 24(12): 40-47.

Department of Chemistry

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