Genetically-Encoded Chemically-Modified Peptides — ASN Events
  1. Schedule
  2. Session 11 - Design
  3. Genetically-Encoded Chemically-Modified Peptides

Genetically-Encoded Chemically-Modified Peptides (#57)

Ratmir Derda 1
  1. University of Alberta, Edmonton, AB, Canada

Genetically-encoded (GE) libraries of proteins and peptides are the major source of discovery of biological drugs and development of ligands. Selection of peptide and protein sequences from GE-libraries of billion-scale diversity is routine both in academia and industry. These techniques, however, have been limited to handling of structures made of 20 natural amino acids. Our group uses GE-libraries of peptides as a starting material for multi-step organic synthesis to produce GE-libraries of peptide derivatives. We developed the methodology for quantification of yield, purity and kinetics of reactions on phage-displayed peptide libraries.2b Examples are N-terminal conjugation1 and cyclization of linear peptides2 with simultaneous introduction of glycan entities. These chemical modifications allowed us to develop Genetically-Encoded Fragment-Based Discovery (GE-FBD) platform,3 which combines >108 peptide fragments with variable, silently-encoded modifications.4 The talk will highlight the advances in application of GE-FBD platform to carbohydrate binding proteins, such as ConA,3 Galectins, DC-SIGN and anti-LAM antibodies. I will also share new technologies we developed to accelerate discovery within any genetically-encoded library framework and maximize the reproducibility of discovery.

 

  1. 1. (a) J. Am. Chem. Soc., 2014, 136, 8149. (b) ACS Chem. Biol., 2012, 7, 1482
  2. 2. (a) ACS Chem. Biol., 2014, 9, 443; (b) Chem. Sci., 2016, 7, 3785; (c) Org. Biomol. Chem., 2016, 14, 5539.
  3. 3. J. Am. Chem. Soc., 2015, 137, 5248
  4.  4. J. Am. Chem. Soc., 2016, 138, 32.