The rapid development of antimicrobial resistance is pushing the search in the discovering of novel antimicrobial molecules to prevent and treat bacterial infections. Self-assembling antimicrobial peptides, as the lipidated peptides, are a novel and promising class of molecules capable of meeting this need. Based on previous work on Temporin L analogs, several new molecules lipidated at the N- or and the C-terminus were synthesised. Our goal is to improve membrane interactions through finely tuning self-assembly to reduce oligomerisation in aqueous solution and enhance self-assembly in bacterial membranes while reducing toxicity against human cells. The results here reported show that the length of the aliphatic moiety is a key factor to control target cell specificity and the oligomeric state of peptides either in aqueous solution or in a membrane-mimicking environment. The results of this study pave the way for the design of novel molecules with enhanced activities.

抗菌素耐药性的迅速发展推动了寻找预防和治疗细菌感染的新型抗菌素分子的探索。自组装抗微生物肽，如脂化肽，是能够满足这一需求的新型且有希望的分子。基于Temporin L类似物的先前工作，合成了在N端和C端脂化的几个新分子。我们的目标是通过微调自组装以减少水溶液中的低聚并增强细菌膜的自组装，同时减少对人体细胞的毒性来改善膜的相互作用。此处报道的结果表明，脂族部分的长度是控制靶细胞特异性和水溶液或膜模拟环境中肽的寡聚状态的关键因素。这项研究的结果为设计具有增强活性的新型分子铺平了道路。