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碳水化合物-蛋白质相互作用和多价性:对抑制甲型流感病毒感染的影响。

Carbohydrate-protein interactions and multivalency: implications for the inhibition of influenza A virus infections.

机构信息

a Department of Chemical Biology & Drug Discovery , Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Utrecht , The Netherlands.

出版信息

Expert Opin Drug Discov. 2019 Apr;14(4):387-395. doi: 10.1080/17460441.2019.1573813. Epub 2019 Feb 5.

Abstract

Protein-carbohydrate interactions play a very important role in many biological processes. A single interaction between a protein and a carbohydrate is usually weak, but multivalent ligands can compensate for this deficiency by binding multiple binding sites to one biological entity simultaneously. Over the past few years, numerous efforts have been made for the design and synthesis of carbohydrate-based multivalent ligands thereby serving as potent inhibitors for pathogens such as the influenza A virus. Areas covered: In this review, the authors cover a variety of multivalent systems from small to large molecules which showed a potent inhibitory effect against several pathogens. Expert opinion: Scaffold structure, linker type, and ligand density are important parameters that need to be optimized for potent multivalent inhibitors. The challenges of multivalent glycodrugs include issues such as bioavailability, pharmacokinetics, and immunogenicity which greatly depend on where the compounds are used in the body. Anti-flu (influenza) applications in the lungs using multivalent carbohydrates particularly has potential because of the high binding affinities. With much more research focusing on Influenza A virus inhibition, therapeutic applications may be achieved in the near future.

摘要

蛋白质-碳水化合物相互作用在许多生物过程中起着非常重要的作用。蛋白质和碳水化合物之间的单一相互作用通常很弱,但多价配体可以通过同时结合多个结合位点到一个生物实体上来弥补这种缺陷。在过去的几年中,人们已经做出了许多努力来设计和合成基于碳水化合物的多价配体,从而作为有效的抑制剂来对抗流感 A 病毒等病原体。

涵盖领域

在这篇综述中,作者涵盖了从小分子到大分子的各种多价系统,这些系统对几种病原体表现出了强大的抑制作用。

专家意见

支架结构、连接子类型和配体密度是需要优化的重要参数,以获得有效的多价抑制剂。多价糖药物的挑战包括生物利用度、药代动力学和免疫原性等问题,这些问题在很大程度上取决于化合物在体内的使用部位。多价碳水化合物在肺部的抗流感(流感)应用具有很大的潜力,因为它们具有很高的结合亲和力。随着对流感 A 病毒抑制的研究越来越多,治疗应用可能在不久的将来实现。

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