He Jian, Eckert Randal, Pharm Thanh, Simanian Maurice D, Hu Chuhong, Yarbrough Daniel K, Qi Fengxia, Anderson Maxwell H, Shi Wenyuan
UCLA School of Dentistry, Department of Microbiology, Immunology, and Molecular Genetics, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, USA.
Antimicrob Agents Chemother. 2007 Apr;51(4):1351-8. doi: 10.1128/AAC.01270-06. Epub 2007 Feb 12.
Streptococcus mutans, a common oral pathogen and the causative agent of dental caries, has persisted and even thrived on the tooth surface despite constant removal and eradication efforts. In this study, we generated a number of synthetic antimicrobial peptides against this bacterium via construction and screening of several structurally diverse peptide libraries where the hydrophobicity and charge within each library was varied incrementally in order to generate a collection of peptides with different biochemical characteristics. From these libraries, we identified multiple peptides with robust killing activity against S. mutans. To further improve their effectiveness, the most bactericidal peptides from each library were synthesized together as one molecule, in various combinations, with and without a flexible peptide linker between each antimicrobial region. Many of these "fusion" peptides had enhanced killing activities in comparison with those of the original nonconjoined molecules. The results presented here illustrate that small libraries of biochemically constrained peptides can be used to generate antimicrobial peptides against S. mutans, several of which may be likely candidates for the development of anticaries agents.
变形链球菌是一种常见的口腔病原体，也是龋齿的致病因子，尽管人们不断努力清除和根除它，但它仍在牙齿表面持续存在甚至大量繁殖。在本研究中，我们通过构建和筛选几个结构多样的肽库，针对这种细菌生成了多种合成抗菌肽，每个肽库中的疏水性和电荷以递增方式变化，以生成具有不同生化特性的肽集合。从这些肽库中，我们鉴定出了多种对变形链球菌具有强大杀伤活性的肽。为了进一步提高它们的有效性，将每个肽库中杀菌能力最强的肽以各种组合方式合成为一个分子，在每个抗菌区域之间有或没有柔性肽接头。与原始的非连接分子相比，许多这些“融合”肽具有增强的杀伤活性。此处呈现的结果表明，受生化限制的小肽库可用于生成针对变形链球菌的抗菌肽，其中几种可能是开发防龋剂的潜在候选物。
