Kang Sung-Min, Moon Heejo, Han Sang-Woo, Kim Byeong Wook, Kim Do-Hee, Kim Byeong Moon, Lee Bong-Jin
College of Pharmacy, Duksung Women's University, Seoul 01369, Korea.
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.
Microorganisms. 2021 Mar 10;9(3):568. doi: 10.3390/microorganisms9030568.
The structure-function relationships of toxin-antitoxin (TA) systems from have prompted the development of novel and effective antimicrobial agents that selectively target this organism. The artificial activation of toxins by peptide inhibitors can lead to the growth arrest and eventual death of bacterial cells. Optimizing candidate peptides by hydrocarbon α-helix stapling based on structural information from the VapBC TA system and in vitro systematic validation led to , a VapC26 activator of . This compound exhibited highly enhanced activity and cell permeability owing to the stabilizing helical propensity of the peptide. These characteristics will increase its efficacy against multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Similar approaches utilizing structural and biochemical information for new antibiotic targets opens a new era for developing TB therapies.
来自[具体来源未提及]的毒素-抗毒素（TA）系统的结构-功能关系促使了新型有效抗菌剂的开发，这些抗菌剂能选择性地靶向该生物体。肽抑制剂对毒素的人工激活可导致细菌细胞生长停滞并最终死亡。基于VapBC TA系统的结构信息通过烃α-螺旋钉合优化候选肽并进行体外系统验证，得到了[具体名称未提及]，一种[具体物质未提及]的VapC26激活剂。由于该肽具有稳定的螺旋倾向，该化合物表现出高度增强的活性和细胞通透性。这些特性将提高其对耐多药结核病和广泛耐药结核病的疗效。利用新抗生素靶点的结构和生化信息的类似方法为开发结核病治疗方法开启了一个新时代。
