Chemical synthesis of homogeneous glycopeptides and glycoproteins

Abstract

Oligosaccharides linked to proteins are known to play important roles in several biological events. However, oligosaccharides are heterogeneous, which has hindered detailed elucidation of oligosaccharide functions. In order to solve this problem, glycoproteins having homogeneous oligosaccharides have long been required. For this purpose, an effi cient preparative method of complex-type oligosaccharides has been investigated from a natural source and this method was found to afford over 24 kinds of diverse complex-type oligosaccharides by use of chemical methods and branch-specifi c sequential glycosidase digestion. The suffi cient amount of homogeneous complex type oligosaccharides obtained enabled us to examine the synthesis of homogeneous glycopeptides as well as glycoproteins by use of solid phase glycopeptide synthetic method and native chemical ligation. This review describes recent progress related to the effi cient method of oligosaccharide preparation and synthesis of glycoproteins including bioactive erythropoietin.

Hydrogels formed by oxo-ester mediated native chemical ligation

“…2,3 NCL leads to minimal epimerization and byproduct formation and is highly selective to the N -terminal Cys, allowing the use of unprotected, post-translationally modified, and non-naturally occurring amino acids. NCL has been used to synthesize ion channel proteins such as KcsA, 4 the plant protein crambin, 3 glycosylated proteins such as monocyte chemotactic protein-3, 5 and other difficult or otherwise impossible protein sequences.…”

Convergent Chemical Synthesis of [Lysine24, 38, 83] Human Erythropoietin

“…[ 9 ] Recent developments in chemical synthesis of proteins [10] and glycoproteins [11] have made it possible in principle to prepare homogeneous EPO by total synthesis, thus offering the prospect of complete control of the covalent structure in order to perform systematic structure-activity studies. An early synthetic achievement was the preparation of a series of homogeneous polymer-modified EPO analogues of defined covalent structure and full biological activity.…”

Convergent Chemical Synthesis of [Lysine24, 38, 83] Human Erythropoietin

“…The production of homogeneous, glycosylated EPO by total synthesis is a major current objective of the organic synthesis community 9. Recent developments in chemical synthesis of proteins10 and glycoproteins11 have made it possible in principle to prepare homogeneous EPO by total synthesis, thus offering the prospect of complete control of the covalent structure in order to perform systematic structure–activity studies.…”