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.