Biological

Biological Chemistry seminar: Jason Beiger, Amgen

Thu, 2019-04-04 15:00
Location: 

Carolyn Hoff Lynch Room

Host: Dr. Ponzy Lu

 

 

John C. Makris Memorial Lecture

 

Jason Beiger

Amgen

 

"Sulfonamides as Selective Nav1.7 Inhibitors for the Treatment of Pain"

Biological Chemistry seminar: Joseph Han, University of Pennsylvania

Thu, 2018-09-27 15:00 - 16:00
Location: 

Carolyn Hoff Lynch Room

"Dissecting the molecular basis of the Scaffold Protein JADE1 in HBO1 Histone Acetyltransferase (HAT) activity"

Biological Chemistry seminar: David Chenoweth, University of Pennsylvania

Thu, 2018-12-13 15:00 - 16:00
Location: 

Carolyn Hoff Lynch Room

"Rational redesign of the collagen triple helix"

Biological Chemistry seminar: Alan Saghetalian, Salk Institute

Thu, 2019-03-14 15:00
Speaker: 

"Exploring the Human smORFeome"

Determining the number and understanding the function of protein-coding genes in the human genome is one of the most important challenges in biology. Using a combination of cutting-edge proteomics and genomics tools we have found thousands of new protein-coding genes in the human genome. These protein-coding genes were initially missed because they encode proteins of less than a hundred amino acids (microproteins), revealing a blind spot in gene finding algorithms for small ORFs (smORFs). The functional characterization of several smORFs has led to the discovery of new pathways that regulate diverse cellular processes such as DNA repair and mitochondrial function. These results highlight the existence of a large new class of understudied protein-coding genes that should contain many additional bioactive microproteins.

Location: 
Carolyn Hoff Lynch Room

Host:  Dr. Megan Matthews

Biological Chemistry seminar: Binghe Wang, Georgia State University

Thu, 2019-02-21 15:00
Speaker: 

Binghe Wang

Georgia State University

 

"Defying conventional wisdom:  Developing carbon monoxide as a therapeutic agent"

 

Nitric oxide, hydrogen sulfide and carbon monoxide are all very toxic molecules, and yet they belong to the gasotransmitter family of signaling molecules with importance on par with that of neurotransmitters and hormone molecules. Studies have shown that these endogenously produced molecules have a wide range of physiologic roles and therapeutic potentials. Specific functions of these molecules are of course unique for each of them.  While the use of NO-producing molecules as therapeutics has long been established, the exploration of hydrogen sulfide and carbon monoxide as therapeutics is still at its infancy at best. This presentation will discuss issues related to developing carbon monoxide-based therapeutics and possible solutions.

Location: 

Carolyn Hoff Lynch Room

 

Host:  Dr. Ivan Dmochowski

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

Department of Chemistry

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

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

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