Welch Nicholas G, Li Wenyi, Hossain Mohammed Akhter, Separovic Frances, O'Brien-Simpson Neil M, Wade John D
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
School of Chemistry, University of Melbourne, Melbourne, VIC, Australia.
Front Chem. 2020 Dec 1;8:607769. doi: 10.3389/fchem.2020.607769. eCollection 2020.
As we rapidly approach a post-antibiotic era in which multi-drug resistant bacteria are ever-pervasive, antimicrobial peptides (AMPs) represent a promising class of compounds to help address this global issue. AMPs are best-known for their membrane-disruptive mode of action leading to bacteria cell lysis and death. However, many AMPs are also known to be non-lytic and have intracellular modes of action. Proline-rich AMPs (PrAMPs) are one such class, that are generally membrane permeable and inhibit protein synthesis leading to a bactericidal outcome. PrAMPs are highly effective against Gram-negative bacteria and yet show very low toxicity against eukaryotic cells. Here, we review both the PrAMP family and the past and current definitions for this class of peptides. Computational analysis of known AMPs within the DRAMP database (http://dramp.cpu-bioinfor.org/) and assessment of their PrAMP-like properties have led us to develop a revised definition of the PrAMP class. As a result, we subsequently identified a number of unknown and unclassified peptides containing motifs of striking similarity to known PrAMP-based DnaK inhibitors and propose a series of new sequences for experimental evaluation and subsequent addition to the PrAMP family.
随着我们迅速迈入一个后抗生素时代，多重耐药细菌无处不在，抗菌肽（AMPs）成为一类有前景的化合物，有助于解决这一全球性问题。AMPs最为人所知的是其破坏细胞膜的作用方式，可导致细菌细胞裂解和死亡。然而，许多AMPs也已知具有非裂解性且有细胞内作用方式。富含脯氨酸的抗菌肽（PrAMPs）就是这样一类，它们通常可透过细胞膜并抑制蛋白质合成，从而产生杀菌效果。PrAMPs对革兰氏阴性菌高效，而对真核细胞的毒性却非常低。在此，我们综述了PrAMP家族以及此类肽过去和当前的定义。通过对DRAMP数据库（http://dramp.cpu-bioinfor.org/）中已知AMPs的计算分析及其PrAMP样特性评估，我们对PrAMP类进行了修订定义。结果，我们随后鉴定出一些与已知基于PrAMP的DnaK抑制剂具有显著相似基序的未知且未分类的肽，并提出了一系列新序列用于实验评估，随后添加到PrAMP家族中。
