Yang Hao, Yuan Fei, Xie Guangxu, Fu Yinxue, Mi Jia, Yu Longjie, Liu Weijia, Li Yulei
School of Pharmaceutical Sciences & Institute of Materia Medica, State Key Laboratory of Advanced Drug Delivery and Release Systems, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, P. R. China.
Chembiochem. 2025 Jun 16;26(12):e202500204. doi: 10.1002/cbic.202500204. Epub 2025 May 22.
Ocellatin-3N is a cationic, amphiphilic host-defense peptide with 19 residues, which is isolated from the Caribbean frog Leptodactylus nesiotus. Its analogue Oce-3N-0 shows potent inhibitory activity against both Gram-negative and Gram-positive pathogens, and has great potential as a broad-spectrum antimicrobial agent. However, the application of Oce-3N-0 as an antimicrobial agent is limited due to its both unstable structure and susceptibility to degradation by proteases. In this research, a series of hydrocarbon-stable analogs of Oce-3N-0 are synthesized and evaluated for their chemical and biological properties to improve potential application of Oce-3N-0 in the field of antimicrobial drug development. Some analogs show remarkable improvement not only in protease resistance but also in antimicrobial activity when compared to the parent peptide. In particular, the stapled peptide Oce-3N-5 shows promising prospects for novel antimicrobial drug development. This study can provide a reference for the development of antimicrobial drugs.
奥西拉汀 - 3N是一种具有19个残基的阳离子两亲性宿主防御肽，它是从加勒比蛙类物种 Nesiotus leptodactylus中分离出来的。其类似物Oce - 3N - 0对革兰氏阴性菌和革兰氏阳性菌病原体均显示出强大的抑制活性，作为一种广谱抗菌剂具有巨大潜力。然而，由于其结构不稳定且易被蛋白酶降解，Oce - 3N - 0作为抗菌剂的应用受到限制。在本研究中，合成了一系列Oce - 3N - 0的碳氢稳定类似物，并对其化学和生物学性质进行了评估，以改善Oce - 3N - 0在抗菌药物开发领域的潜在应用。与亲本肽相比，一些类似物不仅在蛋白酶抗性方面表现出显著改善，而且在抗菌活性方面也有提高。特别是，环肽Oce - 3N - 5在新型抗菌药物开发方面显示出有前景的前景。本研究可为抗菌药物的开发提供参考。
