Tuesday, April 26, 2016

ChemBio Seminar Series | "Discovery of Functional Ligands from Genetically-Encoded Libraries of Peptide Derivatives"

Dr. Ratmir Derda
Department of Chemistry and Alberta Glycomics Center,
University of Alberta, Canada

Phage display accelerates the discovery of peptide-derived drugs, some of which have been FDA-approved, and many are progressing through the clinical pipeline. However, the building blocks and diversity of phage libraries is limited to amino acids. Our group uses phage display as a foundation for multi-step organic synthesis to produce libraries of peptide derivatives displayed on phage. We developed the methodology for quantification of yield, purity and kinetics of reactions on phage-displayed peptide libraries; examples are N-terminal conjugation1 and cyclization of linear peptides.2 Chemical modification of libraries allowed us to develop Genetically-Encoded Fragment-Based Discovery (GE-FBD) platform,3 which combines >108 peptide fragments with variable, genetically-encoded modifications.4 For example, GE-FBD can be used to select phage-displayed glycopeptides to dock a glycan fragment at the carbohydrate-binding site and guide selection of synergistic peptide motifs adjacent to the pocket.3 We believe that display of peptide derivatives on phage can be developed into an efficient platform for discovery of biological probes and drug leads that combine advantages of small-molecule and “biological” classes of drugs.
1. (a) J. Am. Chem. Soc., 2014, 136, 8149; (b) ACS Chem. Biol., 2012, 7 (9), 1482
2. ACS Chem. Biol., 2014, 9, 443.
3. Ng et al., J. Am. Chem. Soc., 2015, 137, 5248
4. Tjhung et al., J. Am. Chem. Soc., 2016, DOI: 10.1021/jacs.5b10390

Thursday, April 28, 2016
12:30pm in the Seaver Science Auditorium
SSL next to the library

The scientific community is invited to attend.

No comments: