Combinatorial synthesis of MUC1 glycopeptides: Polymer blotting facilitates chemical and enzymatic synthesis of highly complicated mucin glycopeptides
Combinatorial synthesis of MUC1 glycopeptides: Polymer blotting facilitates chemical and enzymatic synthesis of highly complicated mucin glycopeptides
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DOI：
10.1021/ja052521y
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发表时间：
2005-08-24
影响因子：
15
通讯作者：
Nishimura, SI
中科院分区：
文献类型：
--
作者：
Fumoto, M;Hinou, H;Nishimura, SI
基于固相和水溶性聚合物载体之间的“捕获和释放”策略，化学选择性聚合物印迹方法允许快速有效地合成糖肽。我们开发了一种对谷氨酸特异性蛋白酶（BLase）敏感的异双功能连接体。一般程序包括五个步骤，即(i)含有BLase敏感连接体的糖肽的固相合成，（ii）随后的脱保护和从树脂中释放糖肽，（iii）在具有氧胺官能团的水溶性聚合物存在下对糖肽中间体进行化学选择性印迹，（iv）使用糖基转移酶进行糖延伸，(v)通过选择性BLase促进水解从聚合物平台释放目标糖肽。固相化学合成多肽和酶促合成碳水化合物在水溶性聚合物上的结合将极大地促进复杂糖肽文库的生产，从而加强应用研究。我们在这里报告了一种高通量合成系统，用于各种类型的MUC1糖肽，显示出各种糖块。我们相信，这一概念将成为在自动化和组合合成的糖基转移酶反应的基础上合成生物学上重要的糖肽的根深蒂固的曲目的一部分。
The chemoselective polymer blotting method allows for rapid and efficient synthesis of glycopeptides based on a "catch and release" strategy between solid-phase and water-soluble polymer supports. 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 containing BLase 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 polymers with oxylamino functional groups, (iv) sugar elongations using glycosyltransferases, and (v) the release of target glycopeptides from the polymer platform by selective BLase promoted hydrolysis. The combined use of the solid-phase chemical syntheses of peptides and the enzymatic syntheses of carbohydrates on water-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 various types of MUC1 glycopeptides exhibiting a variety of sugar moieties. It is our belief that this concept will become part of the entrenched repertoire for the synthesis of biologically important glycopeptides on the basis of glycosyltransferase reactions in automated and combinatorial syntheses.