Peptide−Sugar Ligation Catalyzed by Transpeptidase Sortase:  A Facile Approach to Neoglycoconjugate Synthesis

Abstract

Glycoconjugate synthesis involving sugar and polypeptide remains a formidable challenge. Here we report a novel enzymatic method involving an unprecedented sortase-catalyzed transamidation reaction for site-specific engineering of sugars into native proteins. We show that sugars appended with a 6-aminohexose moiety can be efficiently ligated to peptides and proteins encoded with a LPXTG sortase recognition sequence. This robust reaction provides an elegant and simple approach for generating neoglycoproteins with an amide-linked sugar moiety at the carboxy terminus.