ACS Chem Biol. 2010 Dec 17;5(12):1097-103. doi: 10.1021/cb100209b. Epub 2010 Oct 8.
Clostridium difficile causes severe hospital-acquired antibiotic-associated diarrhea due to the activity of two large protein toxins. Current treatments suffer from a high relapse rate and are generating resistant strains; thus new methods of dealing with these infections that target the virulence factors directly are of interest. Phage display was used to identify peptides that bind to the catalytic domain of C. difficile Toxin A. Library screening and subsequent quantitative binding and inhibition studies showed that several of these peptides are potent inhibitors. Fragment-based computational docking of these peptides elucidated the binding modes within the active site. These antitoxin peptides may serve as potential lead compounds to further engineer peptidomimetic inhibitors of the clostridial toxins.
艰难梭菌产生的两种大型蛋白毒素导致严重的医院获得性抗生素相关性腹泻。目前的治疗方法存在高复发率和耐药菌株的产生问题；因此，人们对直接针对毒力因子的新方法治疗这些感染产生了兴趣。噬菌体展示技术用于鉴定与艰难梭菌毒素 A 的催化结构域结合的肽。文库筛选和随后的定量结合和抑制研究表明，其中一些肽是有效的抑制剂。这些肽的基于片段的计算对接阐明了在活性位点内的结合模式。这些抗毒素肽可以作为潜在的先导化合物，进一步设计针对梭菌毒素的肽模拟抑制剂。
