Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
J Med Chem. 2012 Aug 23;55(16):7253-61. doi: 10.1021/jm300820a. Epub 2012 Aug 9.
Novel remedies in the battle against multidrug-resistant bacterial strains are urgently needed, and one obvious approach involves antimicrobial peptides and mimics hereof. The impact of α- and β-peptoid as well as β(3)-amino acid modifications on the activity profile against β-lactamase-producing Escherichia coli was assessed by testing an array comprising different types of cationic peptidomimetics obtained by a general monomer-based solid-phase synthesis protocol. Most of the peptidomimetics possessed high to moderate activity toward multidrug-resistant E. coli as opposed to the corresponding inactive peptides. Nevertheless, differences in hemolytic activities indicate that a careful choice of backbone design constitutes a significant parameter in the search for effective cationic antimicrobial peptidomimetics targeting specific bacteria.
急需寻找对抗多药耐药菌的新方法，其中一个明显的方法是使用抗菌肽及其类似物。通过测试一组基于通用单体的固相合成方案获得的不同类型的阳离子肽模拟物，评估了 α-和 β-肽拟肽以及 β(3)-氨基酸修饰对产β-内酰胺酶大肠杆菌活性谱的影响。与相应的无活性肽相比，大多数肽模拟物对多药耐药大肠杆菌具有高至中等的活性。然而，溶血活性的差异表明，在后找针对特定细菌的有效阳离子抗菌肽模拟物时，仔细选择骨架设计是一个重要参数。
