Post-translational Modifications of Natural Antimicrobial Peptides and Strategies for Peptide Engineering.

Post-translational Modifications of Natural Antimicrobial Peptides and Strategies for Peptide Engineering.
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DOI:
10.2174/2211550111201010072
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发表时间:
2012-02
期刊:
Current biotechnology
影响因子:
--
通讯作者:
Wang G
Wang G
中科院分区:
其他
文献类型:
--
作者:
Wang G

文献摘要

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天然抗菌肽(AMPs)是一种由基因编码的防御分子,存在于真细菌、古生菌和真核生物三个生命领域。后者包括原生动物、真菌、植物和动物。现已认识到,氨基酸组成、肽序列和翻译后修饰在很大程度上决定了AMP的结构和功能。本文系统地描述了抗菌肽数据库(http://aps.unmc.edu/AP).)中标注的天然AMP的翻译后修饰目前,在数据库中的1755个AMP中,有1147个被修改并归类为17种以上的类型。通过化学修饰,这些多肽折叠成各种结构支架,这些支架针对细菌表面或细胞内的分子。化学修饰也可以赋予特定的多肽所需的功能。同时,这些修饰还会调节其他多肽的性质,如稳定性。阐明AMP性质与化学修饰的关系对多肽工程具有启迪作用。根据我们设计的目标,可以用不同的方式对多肽进行修饰,以增强所需的特性,同时将不需要的特性降至最低。因此,在将天然AMP发展成为新一代治疗分子的过程中,肽设计起着至关重要的作用。
Natural antimicrobial peptides (AMPs) are gene-coded defense molecules discovered in all the three life domains: Eubacteria, Archaea, and Eukarya. The latter covers protists, fungi, plants, and animals. It is now recognized that amino acid composition, peptide sequence, and post-translational modifications determine to a large extent the structure and function of AMPs. This article systematically describes post-translational modifications of natural AMPs annotated in the antimicrobial peptide database (http://aps.unmc.edu/AP). Currently, 1147 out of 1755 AMPs in the database are modified and classified into more than 17 types. Through chemical modifications, the peptides fold into a variety of structural scaffolds that target bacterial surfaces or molecules within cells. Chemical modifications also confer desired functions to a particular peptide. Meanwhile, these modifications modulate other peptide properties such as stability. Elucidation of the relationship between AMP property and chemical modification inspires peptide engineering. Depending on the objective of our design, peptides may be modified in various ways so that the desired features can be enhanced whereas unwanted properties can be minimized. Therefore, peptide design plays an essential role in developing natural AMPs into a new generation of therapeutic molecules.