Development of convergent methodology to access a broad range of glycopeptides as a firm basis of chemical biology.

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Novel convergent synthetic methodologies to prepare proteins with post-translational modifications were developed. We found out that methylphenacyl thioesters are stable enough to be carried through standard Boc-TFA peptide elongation as a precursor of thioacids, and can be deprotected into the corresponding thioacids easily and cleanly. The thioacids prepared can be converted into amide bonds when treated with N-carbonyl cyclic amino acid anhydrates. We also developed a novel chemical ligation at the site of asparagine using oligopeptides with N-terminal N-Boc-protected beta-thioaspartic acid and C-terminal acyl azide respectively. The reaction proceeds via addition accompanied by loss of nitrogen and sulfur to give the corresponding asymmetrical imide, and deprotection of the Boc group, followed by a spontaneous N to N acyl shift.