Solid-Phase Synthesis of Glycopeptides

Abstract

By considering the inaccessibility of a homogeneous sample from natural sources, a synthetic approach to glycoproteins has been tackled in this laboratory (Nakahara 2003; Hojo and Nakahara 2007). While most of the glycoproteins are too large and complex to be synthesized by a merely chemical procedure, a 20–30 kDa or smaller molecule will be accessible by a combination of solid-phase (glyco)peptide synthesis and segment condensation. Scheme 1 outlines our strategy, which involves (a) synthesis of glycoamino acid building blocks, (b) Fmoc-based solid-phase synthesis, (c) detachment of glycopeptide from the resin synchronized with deprotection of glycan and side-chain functional groups, and (d) segment condensation. In the solid-phase synthesis, the hydroxyl groups of O- or N-glycan are usually masked just as the side-chain functional groups of amino acid to achieve the highest efficiency in every chemical step. On the other hand, minimum protection is desirable in the segment condensation to overcome the poor solubility of the protected (glyco)oligopeptides.