Université de Rennes 1, ICMV, UMR CNRS 6226, 263 Av. du Général Leclerc, F-35042 Rennes Cedex, France.
J Med Chem. 2012 Dec 27;55(24):10885-95. doi: 10.1021/jm3009037. Epub 2012 Dec 6.
De novo cyclic pseudopeptides composed of α-amino and aza-β(3)-amino acids were designed with the aim to obtain potential new antimicrobial agents. Antimicrobial cyclic pseudopeptides (ACPPs) are based on the properties of antimicrobial peptides (AMPs), so they are cationic and amphiphilic. Aza-β(3)-amino acids enhance the in vivo half-life of these compounds and offer the possibility to incorporate a large variety of side chains. Most of the 13 ACPPs exert antimicrobial activities in rich media with broad spectrum of antibacterial activities. Selectivity for bacterial over mammalian cells was determined by testing the hemolytic activities of ACPPs against sheep red blood cells (sRBC). We examined the ratio of cationic to hydrophobic residues as well as the type of hydrophobic side chains essential for biological activity of this class of ACPPs. These results will be useful for designing potential candidates for a therapeutic application.
为了获得有潜力的新型抗菌剂，我们设计了由α-氨基酸和氮杂-β(3)-氨基酸组成的新型环状假肽。抗菌环状假肽（ACPPs）基于抗菌肽（AMPs）的特性，因此它们是阳离子和两亲性的。氮杂-β(3)-氨基酸增强了这些化合物在体内的半衰期，并提供了结合各种侧链的可能性。在富含营养的培养基中，大多数 13 种 ACPP 具有广谱的抗菌活性。通过测试 ACPP 对绵羊红细胞（sRBC）的溶血活性来确定对细菌和哺乳动物细胞的选择性。我们研究了阳离子和疏水性残基的比例以及对该类 ACPPs 的生物活性至关重要的疏水性侧链的类型。这些结果将有助于设计潜在的治疗应用候选物。
