Hong S Y, Oh J E, Kwon M, Choi M J, Lee J H, Lee B L, Moon H M, Lee K H
Protein Chemistry Laboratory, Mogam Biotechnology Research Institute, Kyunggi-Do, 449-910, Korea.
Antimicrob Agents Chemother. 1998 Oct;42(10):2534-41. doi: 10.1128/AAC.42.10.2534.
Novel combinatorial libraries consisting of simplified amino acid sequences were designed to screen for peptides active against the Candida albicans membrane. A novel decapeptide, KKVVFKVKFK, that had a unique primary amino acid sequence was identified in this work. This peptide irreversibly inhibited the growth of C. albicans and showed a broad range of antibacterial activity but no hemolytic activity. Circular dichroism spectra revealed that the predominant secondary structure of this peptide strongly depended on the membrane-mimetic environments; the peptide preferred to form an amphipathic alpha-helical structure in the presence of 50% trifluoroethanol, while it preferred to adopt a distorted alpha-helical structure in the presence of sodium dodecyl sulfate micelles. Experiments in which dye was released from vesicles indicated that this novel antimicrobial peptide killed microorganisms through the action on the membrane as its primary target. Replacement of amino acids in this active decapeptide on the basis of information from the libraries could provide unique information about factors affecting its antimicrobial activity such as its secondary structure, net positive charge, and hydrophobicity.
设计了由简化氨基酸序列组成的新型组合文库，以筛选对白色念珠菌细胞膜有活性的肽。在这项工作中鉴定出一种具有独特一级氨基酸序列的新型十肽KKVVFKVKFK。该肽不可逆地抑制白色念珠菌的生长，并表现出广泛的抗菌活性，但无溶血活性。圆二色光谱显示，该肽的主要二级结构强烈依赖于膜模拟环境；在50%三氟乙醇存在下，该肽倾向于形成两亲性α-螺旋结构，而在十二烷基硫酸钠胶束存在下，它倾向于采用扭曲的α-螺旋结构。从囊泡中释放染料的实验表明，这种新型抗菌肽通过作用于膜作为其主要靶点来杀死微生物。根据文库中的信息替换该活性十肽中的氨基酸，可以提供有关影响其抗菌活性的因素的独特信息，如二级结构、净正电荷和疏水性。
