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.
Matsushita
Takahiko
T
Graduate School of Advanced Life Science and Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Sapporo, Japan.
Nishimura
Shin-Ichiro
S
D000595:Amino Acid Sequence; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D008954:Models, Biological; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*; D013329:Structure-Activity Relationship
D006020:Glycopeptides; D009077:Mucins; D011134:Polysaccharides