Section of Dermatology and Venereology, Department of Clinical Sciences, Lund University, SE-221 84 Lund, Sweden.
Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23 Uppsala, Sweden.
Adv Colloid Interface Sci. 2014 Mar;205:265-74. doi: 10.1016/j.cis.2013.06.009. Epub 2013 Jul 5.
With increasing resistance development against conventional antibiotics, there is an urgent need to identify novel approaches for infection treatment. Antimicrobial peptides may offer opportunities in this context, hence there has been considerable interest in identification and optimization of such peptides during the last decade in particular, with the long-term aim of developing these to potent and safe therapeutics. In the present overview, focus is placed on hydrophobic modifications of antimicrobial peptides, and how these may provide opportunities to combat also more demanding pathogens, including multi-resistant strains, yet not provoking unacceptable toxic responses. In doing so, physicochemical factors affecting peptide interactions with bacterial and eukaryotic cell membranes are discussed. Throughout, an attempt is made to illustrate how physicochemical studies on model lipid membranes can be correlated to result from bacterial and cell assays, and knowledge from this translated into therapeutic considerations.
随着对抗生素的传统耐药性的不断发展，迫切需要寻找新的感染治疗方法。在这种情况下，抗菌肽可能提供了一些机会，因此在过去十年中，人们对这类肽的鉴定和优化产生了浓厚的兴趣，其长期目标是将这些肽开发成有效且安全的治疗药物。在本综述中，重点介绍了抗菌肽的疏水性修饰，以及这些修饰如何为对抗更具挑战性的病原体提供机会，包括多耐药菌株，同时又不会引起不可接受的毒性反应。在这样做的过程中，讨论了影响肽与细菌和真核细胞膜相互作用的物理化学因素。整篇文章试图说明如何将模型脂质膜的物理化学研究与细菌和细胞测定的结果相关联，并将这些知识转化为治疗方面的考虑。
