Wang Guangshun
Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, USA, ;
Curr Biotechnol. 2012 Feb;1(1):72-79. doi: 10.2174/2211550111201010072.
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.
天然抗菌肽(AMPs)是在所有三个生命域中发现的基因编码防御分子:真细菌、古细菌和真核生物。后者涵盖原生生物、真菌、植物和动物。现在人们认识到,氨基酸组成、肽序列和翻译后修饰在很大程度上决定了抗菌肽的结构和功能。本文系统地描述了抗菌肽数据库(http://aps.unmc.edu/AP)中注释的天然抗菌肽的翻译后修饰。目前,数据库中1755种抗菌肽中有1147种经过修饰,并分为17种以上类型。通过化学修饰,这些肽折叠成各种结构支架,靶向细菌表面或细胞内的分子。化学修饰还赋予特定肽所需的功能。同时,这些修饰调节其他肽的特性,如稳定性。阐明抗菌肽特性与化学修饰之间的关系有助于肽工程。根据我们的设计目标,可以以各种方式对肽进行修饰,以便增强所需特征,同时将不需要的特性降至最低。因此,肽设计在将天然抗菌肽开发成新一代治疗分子方面起着至关重要的作用。