Rapid identification of compounds with enhanced antimicrobial activity by using conformationally defined combinatorial libraries
Rapid identification of compounds with enhanced antimicrobial activity by using conformationally defined combinatorial libraries
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DOI：
10.1042/bj3130141
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发表时间：
1996-01-01
影响因子：
4.1
通讯作者：
PerezPaya, E
中科院分区：
文献类型：
--
作者：
Blondelle, SE;Takahashi, E;PerezPaya, E
我们将用于快速鉴定高活性化合物的合成组合库方法的优势与具有特定诱导构象的单个肽的抗菌活性之间关系的先验知识相结合，以便识别相对于起始已知抗菌序列具有增强活性的新肽。在当前的研究中，基于已知在脂质环境中诱导成α螺旋构象的18聚体抗菌肽生成了构象定义的组合文库。不仅可以轻松识别出活性增加 10 倍的新序列，而且在反卷积过程中还获得了有关所研究肽的结构-活性关系的详细信息。通过使用圆二色光谱，发现单个 18 聚体肽在与细胞脂质层和/或唾液酸相互作用时可被诱导成 α-螺旋构象，这可能由于细胞壁脂质堆积的扰动而导致细菌细胞裂解。
We have combined the strength of our synthetic combinatorial library approach for the rapid identification of highly active compounds with prior knowledge of the relationship between the antimicrobial activities of individual peptides with specific induced conformations in order to identify new peptides with enhanced activity relative to a starting known antimicrobial sequence. In the current study, conformationally defined combinatorial libraries were generated based on an 18-mer antimicrobial peptide known to be induced into an a-helical conformation in a lipidic environment. Not only were novel sequences readily identified with 10-fold increases in activity, but detailed information about the structure-activity relationships of the peptides studied was also obtained during the deconvolution process. By using circular dichroism spectroscopy it was found that the individual 18-mer peptides could be induced into alpha-helical conformations on interaction with the cell lipid layer and/or sialic acids, which could result in bacterial cell lysis due to perturbation of the lipid packing of the cell wall.