The novel glycoprotein structure; C-mannosyl tryptophan

Abstract

Glycosylation is one of the most important post- or co-translational modifications of proteins, which affects the biological activities of the parent proteins by influencing the higher-order structure. This modification has been classified into two subtypes: namely N-linked type and O-linked type. Recently, a highly novel variant of glycoproteins that incorporate a C-glycosylated amino acid was identified in various proteins. The total synthesis of one such C-glycosyl amino acid, namely, C2-α -D-C-mannosylpyranosyl-L-tryptophan and related peptides was successfully achieved. The mannose and tryptophan moieties were connected via a ring opening of benzyl-protected 1,2-anhydro-mannose by a lithiated indole derivative. After the functional group conversion and deprotection steps, the glyco-amino acid was synthesized in a concise and stereoselective manner, in high overall yields. Furthermore, intermediate azide acid can serve as a useful building block for peptide elongation. The stereoisomer, C2-α -D-C-glucosylpyranosyl-L-tryptophan was synthesized in a similar way. We describe here the synthesis of C-Man-Trp including by other groups and the possibility of application to clinical methods.