Department of Chemistry, Syracuse University, 111 College Place, Syracuse, NY 13244, USA.
Department of Chemistry & Biochemistry, Rowan University, Glassboro, NJ 08028, USA.
Biomolecules. 2021 Mar 12;11(3):421. doi: 10.3390/biom11030421.
Antimicrobial peptides (AMPs) present a promising scaffold for the development of potent antimicrobial agents. Substitution of tryptophan by non-natural amino acid Azulenyl-Alanine (AzAla) would allow studying the mechanism of action of AMPs by using unique properties of this amino acid, such as ability to be excited separately from tryptophan in a multi-Trp AMPs and environmental insensitivity. In this work, we investigate the effect of Trp→AzAla substitution in antimicrobial peptide buCATHL4B (contains three Trp side chains). We found that antimicrobial and bactericidal activity of the original peptide was preserved, while cytocompatibility with human cells and proteolytic stability was improved. We envision that AzAla will find applications as a tool for studies of the mechanism of action of AMPs. In addition, incorporation of this non-natural amino acid into AMP sequences could enhance their application properties.
抗菌肽 (AMPs) 为开发强效抗菌剂提供了一个有前景的支架。用非天然氨基酸薁基丙氨酸 (AzAla) 取代色氨酸将允许通过利用这种氨基酸的独特性质来研究 AMPs 的作用机制，例如能够在多色氨酸 AMPs 中与色氨酸分开被激发以及对环境不敏感。在这项工作中，我们研究了在抗菌肽 buCATHL4B（含有三个色氨酸侧链）中 Trp→AzAla 取代的效果。我们发现，原始肽的抗菌和杀菌活性得以保留，同时与人细胞的细胞相容性和蛋白水解稳定性得到了提高。我们设想 AzAla 将作为研究 AMPs 作用机制的工具得到应用。此外，将这种非天然氨基酸掺入 AMP 序列中可以增强它们的应用性能。
