Blondelle S E, Takahashi E, Weber P A, Houghten R A
Torrey Pines Institute for Molecular Studies, San Diego, California 92121.
Antimicrob Agents Chemother. 1994 Oct;38(10):2280-6. doi: 10.1128/AAC.38.10.2280.
The use of water-soluble synthetic peptide combinatorial libraries permits the systematic examination of tens to hundreds of millions of peptides in existing microdilution assays. In the present study, we prepared and determined the antistaphylococcal activities of two new synthetic peptide combinatorial libraries (one N-acetylated, the other not) composed of tetrapeptides having one position defined and the remaining three positions made up of mixtures of L-, D-, and unnatural amino acids (a total of 58 different amino acids). These libraries, when used in conjunction with an iterative selection process, allowed for the development of a series of individually defined tetrapeptides with high levels of activity against Staphylococcus aureus. The activities of the final individual peptides against two additional strains of gram-positive bacteria (methicillin-resistant S. aureus and Streptococcus sanguis), a gram-negative bacterium (Escherichia coli), as well as the yeast Candida albicans were also determined. Cell viability assays showed that the identified peptides are bacteriostatic against both S. aureus and E. coli.
使用水溶性合成肽组合文库能够在现有的微量稀释试验中系统地检测数千万至数亿种肽。在本研究中，我们制备并测定了两个新的合成肽组合文库（一个N-乙酰化，另一个未乙酰化）的抗葡萄球菌活性，这些文库由四肽组成，其中一个位置确定，其余三个位置由L-、D-和非天然氨基酸混合物（总共58种不同氨基酸）组成。当这些文库与迭代筛选过程结合使用时，能够开发出一系列对金黄色葡萄球菌具有高活性的、单独定义的四肽。还测定了最终单个肽对另外两种革兰氏阳性菌（耐甲氧西林金黄色葡萄球菌和血链球菌）、一种革兰氏阴性菌（大肠杆菌）以及酵母白色念珠菌的活性。细胞活力测定表明，所鉴定的肽对金黄色葡萄球菌和大肠杆菌均具有抑菌作用。
