Strategies and Tactics for the Development of Selective Glycan-Binding Proteins.

Strategies and Tactics for the Development of Selective Glycan-Binding Proteins.
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DOI:
10.1021/acschembio.0c00880
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发表时间:
2021-10-15
影响因子:
4
通讯作者:
Imperiali, Barbara
Imperiali, Barbara
中科院分区:
生物学2区
文献类型:
--
作者:
Ward, Elizabeth M.;Kizer, Megan E.;Imperiali, Barbara

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多糖对所有生物过程、疾病状态和致病相互作用都有影响。糖链结合蛋白(GBP),如凝集素,是研究糖链结构和功能的决定性工具,因为它们易于使用,并且能够选择性地结合已定义的碳水化合物表位和糖苷键。GBP试剂是基础研究、临床诊断、治疗和生物技术应用的重要工具。然而,由于缺乏特异性和选择性的蛋白质试剂来覆盖自然界中存在的大量多样性的碳水化合物结构,对多糖的研究受到了阻碍。此外,现有的GBP试剂往往亲和力低或特异性广,使数据解释复杂化。为了改进现有GBP的特性或设计新的特异性和潜在的应用,人们已经做出了许多努力,试图通过蛋白质工程将GBP工具包扩展到从自然来源确定的那些之外。本文详细介绍了目前结合碳水化合物的蛋白质的范围,以及已应用于提高结合剂的亲和力、选择性和特异性的工程方法。
The influences of glycans impinge on all biological processes, disease states and pathogenic interactions. Glycan-binding proteins (GBPs), such as lectins, are decisive tools for interrogating glycan structure and function because of their ease of use and ability to selectively bind defined carbohydrate epitopes and glycosidic linkages. GBP reagents are prominent tools for basic research, clinical diagnostics, therapeutics, and biotechnological applications. However, the study of glycans is hindered by the lack of specific and selective protein reagents to cover the massive diversity of carbohydrate structures existing in nature. In addition, existing GBP reagents often suffer from low affinity or broad specificity, complicating data interpretation. There have been numerous efforts to expand the GBP toolkit beyond those identified from natural sources through protein engineering, in order to improve the properties of existing GBPs or to engineer novel specificities and potential applications. This review details the current scope of proteins that bind carbohydrates and the engineering methods that have been applied to enhance affinity, selectivity, and specificity of binders.
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