Novel synthesis of functional mucin glycopeptides containing both N- and O-glycans.

Progress of synthetic methods using ligation makes it possible to access larger and multifunctionalized biomolecules. Recently, sortase-mediated ligation was used as a new and complementary technique for construction of peptide and protein to other ligation methods. Staphylococcus aureus Sortase A (SrtA) is a transpeptidase that recognizes C-terminal LPXTG motif of proteins to cleave between T and G, and subsequently transfers the acyl component to a nucleophile containing N-terminal oligo-glycines. Toward development of multi- and heteroglycosylated protein synthesis, we utilized SrtA-mediated ligation technique for preparation of MUC1-related glycopeptide analogs having both N- and O-glycans as model compounds. To further improve this synthetic strategy, we also demonstrated the merits of SrtA-mediated ligation by means of a polymer-supported protocol. The present strategy will facilitate rapid and large-scale synthesis of multiply functionalized neoglycoprotein as new types of convenient models for the investigation of structure-function relationship. Copyright (c) 2010 Elsevier Inc. All rights reserved.