Kang Su-Jin, Won Hyung-Sik, Choi Wahn-Soo, Lee Bong-Jin
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
J Pept Sci. 2009 Sep;15(9):583-8. doi: 10.1002/psc.1149.
De novo design of amphipathic model peptides has been successful for generating many antimicrobial peptides with various lengths and amino acid compositions. Here, we suggest a very simple strategy to design antimicrobial peptides with a short length and a simple amino acid composition. Amphipathic helical properties were conferred by using only leucines and lysines and a single tryptophan was positioned at the critical amphipathic interface between the hydrophilic ending side and the hydrophobic starting side, in the helical wheel projection. According to this rule, the model peptides with 7 to 13 residues exhibited antimicrobial activity. Among them, the most potent activity against both Gram-positive and Gram-negative bacteria, covering all of the nine bacterial strains tested in this study, was found for the 11-mer sequences having a 1:1 (L(5)K(5)W(6)) or a 3:2 (L(6)K(4)W(6)) ratio of leucines to lysines. In particular, the former peptide L(5)K(5)W(6) could be evaluated as the most useful agent, as it showed no significant hemolytic activity with a broad-spectrum of antimicrobial activity.
从头设计两亲性模型肽已成功生成了许多具有不同长度和氨基酸组成的抗菌肽。在此，我们提出一种非常简单的策略来设计具有短长度和简单氨基酸组成的抗菌肽。通过仅使用亮氨酸和赖氨酸赋予两亲性螺旋特性，并且在螺旋轮投影中，一个色氨酸位于亲水末端侧和疏水起始侧之间的关键两亲性界面处。根据此规则，具有7至13个残基的模型肽表现出抗菌活性。其中，对于亮氨酸与赖氨酸比例为1:1（L(5)K(5)W(6)）或3:2（L(6)K(4)W(6)）的11聚体序列，发现其对革兰氏阳性菌和革兰氏阴性菌均具有最强活性，涵盖了本研究中测试的所有九种细菌菌株。特别是，前一种肽L(5)K(5)W(6)可被视为最有用的药剂，因为它具有广谱抗菌活性且无明显溶血活性。
