This invention discloses a method and application for the chemical
enzymatic synthesis of O-glycopeptides, belonging to the field of
pharmaceutical technology. The method includes the following steps: assembling a polypeptide intermediate using a
solid-phase polypeptide synthesis method, wherein the amino acids at non-glycosylated active sites in the polypeptide intermediate are protected by sterically hindered protecting groups, while the hydroxyl groups on the amino acids at predetermined
glycosylation sites are unprotected;
glycosylation of the polypeptide intermediate with a glyconucleotide donor in the presence of a
glycosyltransferase to obtain a
glycopeptide intermediate; and reacting the
glycopeptide intermediate with a deprotecting agent to remove the sterically hindered protecting groups, thus obtaining the target
glycopeptide. This invention uses amino acids modified with protecting groups as raw materials, selectively protects the active hydroxyl sites in the amino acids, prepares polypeptide intermediates through
solid-phase polypeptide synthesis, efficiently and accurately synthesizes the target glycopeptide intermediate with the help of
glycosyltransferase synergistic catalysis, and finally obtains the target glycopeptide by removing the protecting groups through a catalyst.