Nature-inspired protein ligation and its applications.

Nature-inspired protein ligation and its applications.
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DOI:
10.1038/s41570-023-00468-z
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发表时间:
2023-04
影响因子:
36.3
通讯作者:
David, Yael
David, Yael
中科院分区:
化学1区
文献类型:
--
作者:
Pihl, Rasmus;Zheng, Qingfei;David, Yael

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操纵蛋白质和肽的化学组成的能力一直是开发改进的基于多肽的治疗方法的核心,并使研究人员能够解决基本的生物学问题,否则这些问题将无法解决。蛋白质连接,其中两个或更多个多肽共价连接,是用于产生半合成产物和用于控制多肽拓扑结构的有力策略。然而,需要专门的工具以快速动力学和高产率的化学选择性方式有效地锻造肽键。幸运的是,大自然已经通过进化酶机制解决了这一挑战,这些酶机制可以使用各种化学反应连接多肽。在这里,我们总结了这种自然启发的蛋白质连接策略已被重新利用为化学生物学工具,提供增强控制多肽组成。
The ability to manipulate the chemical composition of proteins and peptides has been central to the development of improved polypeptide-based therapeutics and has enabled researchers to address fundamental biological questions that would otherwise be out of reach. Protein ligation, in which two or more polypeptides are covalently linked, is a powerful strategy for generating semisynthetic products and for controlling polypeptide topology. However, specialized tools are required to efficiently forge a peptide bond in a chemoselective manner with fast kinetics and high yield. Fortunately, nature has addressed this challenge by evolving enzymatic mechanisms that can join polypeptides using a diverse set of chemical reactions. Here, we summarize how such nature-inspired protein ligation strategies have been repurposed as chemical biology tools that afford enhanced control over polypeptide composition.
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