Combinatorial Synthesis of MUC1 Glycopeptides: Polymer Blotting Facilitates Chemical and Enzymatic Synthesis of Highly Complicated Mucin Glycopeptides

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• 作者：Masataka Fumoto ; Hiroshi Hinou ; Takashi Ohta ; Takaomi Ito ; Kuriko Yamada ; Akio Takimoto ; Hirosato Kondo ; Hiroki Shimizu ; Toshiyuki Inazu ; Yoshiaki Nakahara ; and Shin-Ichiro Nishimura
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：August 24, 2005
• 年：2005
• 卷：127
• 期：33
• 页码：11804 - 11818
• 全文大小：556K
• 年卷期：v.127,no.33(August 24, 2005)
• ISSN：1520-5126

文摘

The chemoselective polymer blotting method allows for rapid and efficient synthesis ofglycopeptides based on a "catch and release" strategy between solid-phase and water-soluble polymersupports. We have developed a heterobifunctional linker sensitive to glutamic acid specific protease (BLase).The general procedure consists of five steps, namely (i) the solid-phase synthesis of glycopeptide containingBLase sensitive linker, (ii) subsequent deprotections and the release of the glycopeptide from the resin,(iii) chemoselective blotting of the glycopeptide intermediates in the presence of water-soluble polymerswith oxylamino functional groups, (iv) sugar elongations using glycosyltransferases, and (v) the release oftarget glycopeptides from the polymer platform by selective BLase promoted hydrolysis. The combineduse of the solid-phase chemical syntheses of peptides and the enzymatic syntheses of carbohydrates onwater-soluble polymers would greatly contribute to the production of complicated glycopeptide libraries,thereby enhancing applicative research. We report here a high-throughput synthetic system for the varioustypes of MUC1 glycopeptides exhibiting a variety of sugar moieties. It is our belief that this concept willbecome part of the entrenched repertoire for the synthesis of biologically important glycopeptides on thebasis of glycosyltransferase reactions in automated and combinatorial syntheses.