General

Biological Chemistry seminar: John S. Schneekloth, Jr. (Jay), National Cancer Institute-Frederick

Thu, 2019-02-07 15:00
Speaker: 

John S. Schneekloth, Jr. (Jay)

National Cancer Institute-Frederick

 

"Targeting Structurally and Functionally Diverse Nucleic Acids with Druglike Small Molecules" 

 

The past twenty years have seen an explosion of interest in the structure and function of RNA and DNA.  We now know that while some 80% of the human genome is transcribed into RNA, just ~3% of those transcripts code for protein sequences.  Noncoding RNAs and DNAs have been demonstrated to regulate gene expression and other biological regulatory processes. The deregulation of these RNAs is now known to be causative in a variety of human diseases, ranging from cancer to bacterial and viral infection.  However, efforts to target RNA and DNA with small molecules have lagged far behind protein targets.  Here we discuss our group’s efforts to target RNA and DNA with druglike small molecules using a Small Molecule Microarray (SMM) screening platform. We demonstrate that by rapidly screening a variety of diverse folded nucleic acids targets such as G-quadruplexes and pseudoknot-containing riboswitches, it is possible to identify selective small molecule hits suitable for further study. Furthermore, structural approaches including biomolecular NMR and X-Ray crystallography using hits from SMM screens highlight the potential for structure-guided design on RNA and DNA related to cancer and infectious disease. In this talk, I will discuss in detail our efforts aimed toward designing potent and selective druglike compounds that modulate the expression of MYC by binding to the MYC G-quadruplex, and more recent efforts in targeting the PreQ1 riboswitch. 

Location: 

Carolyn Hoff Lynch Room

 

Host:  Dr. David Chenoweth

Biological Chemistry seminar: Amanda E. Hargrove, Duke University

Thu, 2019-01-24 15:00
Speaker: 

Amanda Hargrove

Duke University

 

"Deciphering patterns in selective small molecule:RNA interactions" While small molecules offer a unique opportunity to target structural and regulatory elements in therapeutically relevant RNAs, selectivity has been a recurrent challenge in small molecule:RNA recognition. In particular, RNAs tend to be more dynamic and offer less chemical functionality than proteins, and biologically active ligands must compete with the highly abundant and highly structured RNA of the ribosome. Indeed, no small molecule drugs targeting RNAs other than the ribosome are currently available, and our recent survey of the literature revealed little more than one hundred reported chemical probes that target non-ribosomal RNA in biological systems. As part of our efforts to improve small molecule targeting strategies and gain fundamental insights into small molecule:RNA recognition, we are analyzing patterns in both RNA-biased small molecule chemical space and RNA topological space privileged for differentiation. To begin, we identified physicochemical, structural, and spatial properties of biologically active RNA ligands that are distinct from those of protein-targeted ligands. Elaboration of four RNA binding scaffolds into a library enriched with these properties has led to improved recognition of medicinally relevant RNA targets, including viral and long noncoding RNA structures. At the same time, we used pattern recognition protocols to identify RNA topologies that can be differentially recognized by small molecules and have elaborated this technique to visualize conformational changes in RNA secondary structure. We are currently expanding these studies with the ultimate goal of applying these insights to the rapid development of ligands with high affinity and specificity for a wide range of RNA targets, particularly those critical to cancer progression.

Location: 

Carolyn Hoff Lynch Room

 

Host:  Dr. David Chenoweth

Biological Chemistry seminar: Jacob Hooker, Harvard University

Thu, 2019-01-17 15:00
Speaker: 

Jacob Hooker

Harvard Medical School

 

"Neurochemical imaging of the human brain with positron emission tomography"


Chemical reactions and interactions dominate human brain function, but unfortunately, we understand poorly the language of this chemical conversation going on in the brain. Although we have some sense for how neurochemicals communicate in cell culture, we have very littleunderstanding of the dynamic relationship between neurochemicals in the living human brain, whether it is at rest, being stimulated, or manipulated by drugs. Positron emission tomography (PET) provides a window into the human brain to study chemistry provided that a radiotracer can be developed to measure molecular interactions.  This seminar will describe the incredible opportunities in PET imaging and the tools that the Hooker Lab has codeveloped to better realize its full potential.


Location: 

Carolyn Hoff Lynch Room

Host: Dr. David Christianson

Biological Chemistry seminar: Karim-Jean Armache, New York University

Thu, 2018-12-06 15:00
Speaker: 

Karim-Jean Armache

New York University School of Medicine

 

"Mechanistic studies of gene silencing complexes"

 

Gene silencing is conserved from yeast to humans, playing a crucial function in establishment, maintenance and propagation of distinct patterns of gene expression. This process plays an essential role in development and its dysregulation can cause diseases including cancer. In all eukaryotes, regulation of gene activity is directed by packaging of DNA into chromatin. The fundamental repeating unit of chromatin is the nucleosome that comprises ~146 base pairs of DNA wrapped around an octamer of histone proteins. The nucleosome is the platform upon which proteins and protein complexes assemble to regulate chromosomal transactions such as gene transcription. These complexes act in part by modifying and/or binding to specific histone modifications. We use biochemical, biophysical and structural approaches to understand the detailed mechanisms of gene silencing complexes, their interplay with posttranslational modifications of histones and their effect on higher-order chromatin structure.

Location: 

Carolyn Hoff Lynch Room

Biological Chemistry seminar: Abhinav Nath, University of Washington

Thu, 2018-11-01 15:00
Location: 

Carolyn Hoff Lynch Room

Topic: Protein molecular dynamics and health

Host: Dr. Elizabeth Rhoades

Biological Chemistry seminar: Kabirul Islam, University of Pittsburgh

Thu, 2018-10-18 15:00
Location: 

Carolyn Hoff Lynch Room

"Protein and small molecule engineering towards an orthogonal chromatin landscape"

Host: Dr. E. James Petersson

Biological Chemistry seminar: Sua Myong, Johns Hopkins University

Thu, 2018-10-11 15:00
Location: 
Carolyn Hoff Lynch Room

"Defective RNA interaction leads to aberrant phase separation of ALS-linked mutant FUS"

Inorganic Chemistry Seminar: Dr. David Goldberg, Johns Hopkins University

Tue, 2019-02-26 12:00 - 13:00
Speaker: 
Dr. David Goldberg
Location: 

Carol Lynch Lecture Hall

Chemistry Complex

 

Title: Heme and Non-heme Transition Metal Complexes: Activation of O2 and NO, and the Reactivity of High-Valent M(O)/M(OH) Species

Organic Chemistry Seminar: Dr. Andrew McNally, Colorado State University

Mon, 2018-11-12 12:00 - 13:00
Speaker: 

Dr. Andrew McNally

Title: Selective Functionalization of Pyridines, Diazine and Pharmaceuticals via Heterocyclic Phosphonium Salts
Abstract: Selective methods that can functionalize electron-deficient heterocycles are in great demand due to their prevalence in biologically active compounds. Pyridines and diazines, in particular, are widespread components of pharmaceutical compounds yet methods to transform these motifs into valuable derivatives are still greatly sought after. We will present a selection of catalytic and non-catalytic methods using  phosphorus intermediates that enable multiple new bond-constructions on these heterocycles. A particular emphasis will be placed on phosphorus ligand-coupling reactions that represent an alternative means to form C–C and C-Heteroatom bonds.
Location: 

Carol Lynch Lecture Hall

Chemistry Complex

Attached Document: 

Host: Dr. Walsh

inquires rvargas@sas.upenn.edu

Inorganic Chemistry Seminar: Dr. Amy Prieto, Colorado State University

Tue, 2018-10-16 12:00 - 13:00
Speaker: 

Dr. Amy Prieto

Title "Inexpensive, Efficient Approaches for Energy Production and Storage"

 

 We are interested in developing new synthetic methods for nanoscale materials with applications in energy conversion and storage. For this talk, I will focus first on using photovoltaic devices to produce energy, and in particular the synthesis and characterization of Cu2ZnSnS4 nanoparticles. The structure-property relationships for these particles can be significantly modified as the metal and chalcogen stoichiometries are tuned.  Second, I’ll discuss our efforts to develop new architectures for rechargeable Li-ion batteries for storing that energy. We are working to incorporate high surface area structures of a novel anode material into a new battery architecture wherein the current collector is conformally coated with an electrolyte made by electrochemical deposition, then surrounded by the cathode electrode. The significant advantage is that the diffusion length for Li+ between the cathode and anode will be dramatically reduced, which should lead to much faster charging rates. The general theme between both topics is the development of new synthetic methods for useful materials with an eye toward non-toxic, earth abundant chemicals and reasonable manufacturing methods.

 

 

M. C. Schulze, R. K. Schulze, A. L. Prieto "Electrodeposited thin-film CuxSb anodes for Li-ion batteries: Enhancement of cycle life via tuning of film composition and engineering of the film-substrate interface" J. Mater. Chem. A20186, 12708-12717.


 

M. Braun, L. Korala, J.  M. Kephart, and A. L. Prieto, “Synthetic Control of Quinary Nanocrystals of a Photovoltaic Material: The Clear Role of Chalcogen Ratio on Light Absorption and Charge Transport for Cu2ZnSn(S1-xSex)4”, ACS Appl. Energy Mater.2018 1(3), 1053-1059.


 

Location: 

Carol Lynch Lecture Hall

Chemistry Complex

Host: Dr Goldberg

inquires rvargas@sas.upenn.edu

Department of Chemistry

231 S. 34 Street, Philadelphia, PA 19104-6323

215.898.8317 voice | 215.573.2112 fax | web@chem.upenn.edu

Syndicate content