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酶促糖苷合成的进展

Advances in Enzymatic Glycoside Synthesis.

作者信息

Danby Phillip M, Withers Stephen G

机构信息

Department of Chemistry, University of British Columbia , Vancouver, British Columbia, Canada.

出版信息

ACS Chem Biol. 2016 Jul 15;11(7):1784-94. doi: 10.1021/acschembio.6b00340. Epub 2016 May 26.

Abstract

A robust platform for facile defined glycan synthesis does not exist. Yet the need for such technology has never been greater as researchers seek to understand the full scope of carbohydrate function, stretching beyond the classical roles of structure and energy storage to encompass highly nuanced cell signaling events. To comprehensively explore and exploit the full diversity of carbohydrate functions, we must first be able to synthesize them in a controlled manner. Toward this goal, traditional chemical syntheses are inefficient while nature's own synthetic enzymes, the glycosyl transferases, can be challenging to express and expensive to employ on scale. Glycoside hydrolases represent a pool of glycan processing enzymes that can be either used in a transglycosylation mode or, better, engineered to function as "glycosynthases," mutant enzymes capable of assembling glycosides. Glycosynthases grant access to valuable glycans that act as functional and structural probes or indeed as inhibitors and therapeutics in their own right. The remodelling of glycosylation patterns in therapeutic proteins via glycoside hydrolases and their mutants is an exciting frontier in both basic research and industrial scale processes.

摘要

目前还不存在一个强大的、便于进行特定聚糖合成的平台。然而,随着研究人员试图全面了解碳水化合物功能的范畴,超越结构和能量储存的经典作用,涵盖高度细微的细胞信号传导事件,对这种技术的需求从未像现在这样迫切。为了全面探索和利用碳水化合物功能的多样性,我们首先必须能够以可控的方式合成它们。为此,传统化学合成效率低下,而自然界自身的合成酶,即糖基转移酶,在表达上可能具有挑战性,大规模使用成本也很高。糖苷水解酶是一类聚糖加工酶,可以以转糖基化模式使用,或者更好的是,经过工程改造后用作“糖合成酶”,即能够组装糖苷的突变酶。糖合成酶使人们能够获得有价值的聚糖,这些聚糖本身可作为功能和结构探针,或者实际上作为抑制剂和治疗剂。通过糖苷水解酶及其突变体对治疗性蛋白质的糖基化模式进行重塑,在基础研究和工业规模生产过程中都是一个令人兴奋的前沿领域。

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