Design and Biosynthesis of Topological Proteins

Ting-ting Yang; Xiao-Di Da; Wen-Bin Zhang

doi:10.11777/j.issn1000-3304.2020.20065

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Design and Biosynthesis of Topological Proteins

更新时间：2021-01-26

- Design and Biosynthesis of Topological Proteins
- Acta Polymerica Sinica Vol. 51, Issue 8, Pages: 804-816(2020)
- 作者机构：
  
  北京分子科学国家研究中心高分子化学与物理教育部重点实验室软物质科学与工程中心北京大学化学与分子工程学院　北京 100871
- 作者简介：
- 基金信息：
- DOI：10.11777/j.issn1000-3304.2020.20065
  CLC：
- Published：2020-8，
  
  Published Online：5 June 2020，
  
  Received：13 March 2020，
  
  Revised：4 April 2020，
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Ting-ting Yang, Xiao-Di Da, Wen-Bin Zhang. Design and Biosynthesis of Topological Proteins. [J]. Acta Polymerica Sinica 51(8):804-816(2020)
DOI：

Ting-ting Yang, Xiao-Di Da, Wen-Bin Zhang. Design and Biosynthesis of Topological Proteins. [J]. Acta Polymerica Sinica 51(8):804-816(2020) DOI： 10.11777/j.issn1000-3304.2020.20065.

摘要

拓扑蛋白质是一类具有复杂拓扑结构的非线性蛋白质，为抗体工程、工程酶、生物材料等领域提供了崭新的研究对象，具有重要的基础科学意义和应用价值. 本专论从拓扑高分子合成的重大挑战出发，总结了天然拓扑蛋白质的合成策略，详细阐述了如何灵活应用组装和反应协同构建人工拓扑蛋白质，讨论了拓扑蛋白质的表征方法，并提出了该领域进一步发展所面临的挑战和机遇.

Abstract

Topological proteins are proteins possessing non-linear backbones and nontrivial chemical topology. Since nascent polypeptide chains are strictly linear as defined by the translational mechanism of the cellular machinery

synthesis of topological proteins remains a huge challenge. By folding into various three-dimensional shapes

proteins can gain certain control over the spatial relationship of secondary motifs

however

the diversity of the chemical topology of the backbone remains largely untapped. The discovery of natural topological proteins in the past decades have inspired the researchers to explore the design and synthesis of artificial topological proteins. Meanwhile

the progresses in supramolecular chemistry and topological polymer chemistry have brought in various strategies for the synthesis of topological molecules in general. Among them

the “assembly-reaction” synergy seems to be a generally applicable and powerful one in creating unconventional structures. With genetically encoded entangling protein motifs and genetically encoded peptide-protein reactive pairs

different topological proteins have been prepared

including cyclic proteins

star proteins

branched proteins

tadpole proteins and protein catenanes. While structures and functions are well preserved in most cases

they also exhibit considerable advantages in terms of thermal stability and resistance to chemical denaturation and proteolytic digestion. Herein

begin with the major challenges in the synthesis of topological polymers

we summarize the biosynthesis of topological proteins in nature and the recent efforts to design and construct artificial topological proteins in chemistry. We will discuss the strategies for their synthesis and characterization

as well as the potential functional benefits of topological proteins. Finally

we will present our perspective on the challenges and opportunities of this emerging field.

关键词

拓扑蛋白质工程打结蛋白套索索烃组装-反应协同

Keywords

TopologyProtein engineeringKnot proteinLassoCatenaneAssembly-reaction synergy

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