“Application of DNA-Encoded Libraries for Academic Drug Discovery”
Dr. Robert A. Welch Chair in Science
Associate Director of the Center for Drug Discovery
Associate Professor in the Department of Biochemistry and Molecular Pharmacology and the Department of Pathology and Immunology
Baylor College of Medicine
Professor bio:
Damian W. Young, Ph.D. is the Robert A. Welch Chair in Science and Associate Director of the Center for Drug Discovery at Baylor College of Medicine. He additionally holds faculty appointments as Associate Professor in the Department of Biochemistry and Molecular Pharmacology and the Department of Pathology and Immunology. He also holds and Adjunct position with the Department of Chemistry at Rice University. Dr. Young’s research is focused on applying principles of modern synthetic organic chemistry to constructing collections of biologically active small molecules for drug discovery. He has applied concepts related to generating molecular diversity within groups of small molecules for modulating a variety of disease-associated biological targets. This has led to the development of chemical probes for interrogating biology and clinical leads for therapeutics. His lab was among the first to apply the principles of diversity generation to fragment-based drug discovery (FBDD) and DNA-Encoded Library (DEL) platforms. Dr. Young received a B.S. in chemistry from Howard University and then worked as a process chemist at Trimeris Inc. on the HIV drug enfuvirtide. He received a Ph.D. in synthetic organic chemistry under the direction of Prof. Daniel Comins at North Carolina State University and subsequently pursued postdoctoral studies in the lab of Prof. Stuart Schreiber at Harvard University and the Broad Institute of MIT and Harvard. Prior to joining Baylor, he was Group Leader within the Chemical Biology Program at the Broad Institute of MIT and Harvard and a Project Leader for the Harvard/Broad Centers of Excellence in Methodology and Library Development (CMLD).
Abstract:
DNA-Encoded Libraries (DELs) involve the chemical barcoding of unique small molecules with unique DNA sequences. A beneficial feature of DELs are their ability to be rapidly screened against a target protein of interest using a simple affinity-based selection format to identify potent binders. Additionally, compared to more conventional forms of screening, DELs offer the advantage of sampling a wider chemical space (10 3 -10 6 more molecules) at a fraction of the cost and time. These features make DELs particularly attractive within the academic community where the target scope can be broad, but also the cost effectiveness of screening is a major limiting factor. We have generated a library containing over 7-billion DNA-encoded molecules which is among the largest collections in academia. We have screened this DEL against emerging academic targets as well as highly validated disease targets of considerable importance to human health. The lecture will focus on these DEL screening efforts and key learnings from them. It will additionally describe future innovations to further expand the utility of the DEL platform.
