Som Abhigyan, Vemparala Satyavani, Ivanov Ivaylo, Tew Gregory N
Department of Polymer Science and Engineering, University of Massachusetts, Amherst, 120 Governors Drive, Amherst, MA 01003, USA.
Biopolymers. 2008;90(2):83-93. doi: 10.1002/bip.20970.
Infectious diseases and antibiotic resistance are now considered the most imperative global healthcare problem. In the search for new treatments, host defense, or antimicrobial, peptides have attracted considerable attention due to their various unique properties; however, attempts to develop in vivo therapies have been severely limited. Efforts to develop synthetic mimics of antimicrobial peptides (SMAMPs) have increased significantly in the last decade, and this review will focus primarily on the structural evolution of SMAMPs and their membrane activity. This review will attempt to make a bridge between the design of SMAMPs and the fundamentals of SMAMP-membrane interactions. In discussions regarding the membrane interaction of SMAMPs, close attention will be paid to the lipid composition of the bilayer. Despite many years of study, the exact conformational aspects responsible for the high selectivity of these AMPs and SMAMPs toward bacterial cells over mammalian cells are still not fully understood. The ability to design SMAMPs that are potently antimicrobial, yet nontoxic to mammalian cells has been demonstrated with a variety of molecular scaffolds. Initial animal studies show very good tissue distribution along with more than a 4-log reduction in bacterial counts. The results on SMAMPs are not only extremely promising for novel antibiotics, but also provide an optimistic picture for the greater challenge of general proteomimetics.
传染病和抗生素耐药性如今被视为全球最紧迫的医疗保健问题。在寻找新的治疗方法、宿主防御或抗菌药物的过程中，肽因其各种独特特性而备受关注；然而，开发体内疗法的尝试受到了严重限制。在过去十年中，开发抗菌肽合成模拟物（SMAMPs）的努力显著增加，本综述将主要关注SMAMPs的结构演变及其膜活性。本综述将试图在SMAMPs的设计与SMAMP-膜相互作用的基本原理之间架起一座桥梁。在讨论SMAMPs的膜相互作用时，将密切关注双层膜的脂质组成。尽管经过多年研究，但这些抗菌肽和SMAMPs对细菌细胞比对哺乳动物细胞具有高选择性的确切构象方面仍未完全了解。利用各种分子支架已证明能够设计出对哺乳动物细胞无毒但具有强效抗菌作用的SMAMPs。初步的动物研究表明其具有非常好的组织分布，细菌数量减少超过4个对数级。关于SMAMPs的研究结果不仅对新型抗生素极具前景，也为更具挑战性的通用蛋白质模拟物提供了乐观的前景。
