Department of Chemistry, East Carolina University, Science and Technology Building, Greenville, NC 27858, USA.
Bioorg Med Chem. 2013 Jan 1;21(1):205-14. doi: 10.1016/j.bmc.2012.10.039. Epub 2012 Nov 1.
A series of 36 synthetic antimicrobial peptides containing unnatural amino acids were screened to determine their effectiveness to treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pnemoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens, which are known to commonly infect chronic wounds. The primary amino acid sequences of these peptides incorporate either three or six dipeptide units consisting of the unnatural amino acids Tetrahydroisoquinolinecarboxylic acid (Tic) and Octahydroindolecarboxylic acid (Oic). The Tic-Oic dipeptide units are separated by SPACER amino acids with specific physicochemical properties that control how these peptides interact with bacterial cell membranes of different chemical compositions. These peptides exhibited minimum inhibitory concentrations (MIC) against these pathogens in the range from >100 to 6.25 μg/mL. The observed diversity of MIC values for these peptides against the various bacterial strains are consistent with our hypothesis that the complementarity of the physicochemical properties of the peptide and the lipid of the bacteria's cell membrane determines the resulting antibacterial activity of the peptide.
研究人员筛选了一系列含有非天然氨基酸的 36 种合成抗菌肽，以确定它们对治疗粪肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌科（ESKAPE）病原体的有效性。这些病原体通常会感染慢性伤口。这些肽的一级氨基酸序列中包含三个或六个二肽单元，由非天然氨基酸四氢异喹啉羧酸（Tic）和八氢吲哚羧酸（Oic）组成。Tic-Oic 二肽单元由具有特定物理化学性质的 SPACER 氨基酸隔开，这些性质控制着这些肽与不同化学成分的细菌细胞膜的相互作用方式。这些肽对这些病原体的最小抑菌浓度（MIC）范围为>100 至 6.25μg/ml。这些肽对不同细菌菌株的 MIC 值的多样性观察结果与我们的假设一致，即肽的物理化学性质与细菌细胞膜的脂质之间的互补性决定了肽的抗菌活性。
