Glycopeptides are peptides that contain carbohydrate moieties (glycans) covalently attached to the side chains of peptide amino acids. Since glycans are present at cell surfaces, these constructs are being explored for a wide array of therapeutic functions such as new antibiotics. Current peptide synthetic routes including solid-phase peptide synthesis (SPPS) and N-carboxyanhydride ring-opening polymerization (NCA-ROP) pose scale-up and cost limitations. In contrast, protease-catalyzed peptide synthesis (PCPS) is conducted under mild conditions (i.e. in water, at 30-40<sup>o</sup>C) generally without protection-deprotection steps. It holds the potential for cost-effective green peptide synthesis that can be scaled making peptides available for applications that are more cost sensitive. This presentation describes a strategy by which glycans are first conjugated to the amino group of an L-α-amino acid to increase the glycan recognition at the protease S1 site. The formation of a glycan-L-α-amino acid acyl enzyme complex can lead to its functioning as a ‘grafter’ that reacts with an incoming amino acid or peptide chain to form the glycopeptide conjugate. The focus of these studies has been to determine how the glycan structure and linkage-chemistry used to form the grafter influences the efficiency of glycopeptide formation.

Protease-catalyzed synthesis of glycopeptides

ACS Spring Meeting 2021

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