Toxin-Activating Stapled Peptides Discovered by Structural Analysis Were Identified as New Therapeutic Candidates That Trigger Antibacterial Activity against Mycobacterium tuberculosis in the Mycobacterium smegmatis Model.
Toxin-Activating Stapled Peptides Discovered by Structural Analysis Were Identified as New Therapeutic Candidates That Trigger Antibacterial Activity against Mycobacterium tuberculosis in the Mycobacterium smegmatis Model.
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DOI：
10.3390/microorganisms9030568
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发表时间：
2021-03-10
期刊：
影响因子：
4.5
通讯作者：
Lee BJ
中科院分区：
文献类型：
--
作者：
Kang SM;Moon H;Han SW;Kim BW;Kim DH;Kim BM;Lee BJ
结核分枝杆菌毒素-抗毒素（TA）系统的结构-功能关系促使了选择性靶向该生物体的新型有效抗菌剂的开发。肽抑制剂对毒素的人工活化可导致细菌细胞的生长停滞和最终死亡。基于来自VapBC TA系统的结构信息和体外系统验证，通过碳氢化合物α-螺旋钉合优化候选肽，得到了M的VapC 26激活剂V26-SP-8。结核由于肽的稳定螺旋倾向，该化合物表现出高度增强的活性和细胞渗透性。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。利用结构和生物化学信息寻找新抗生素靶点的类似方法为开发结核病疗法开辟了新时代。
The structure-function relationships of toxin-antitoxin (TA) systems from Mycobacterium tuberculosis 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 V26-SP-8, a VapC26 activator of M. tuberculosis. 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.
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影响因子：
14.9
作者：
Kim DH;Kang SM;Park SJ;Jin C;Yoon HJ;Lee BJ
通讯作者：
Lee BJ
影响因子：
7.3
作者：
Kang, Sung-Min;Jin, Chenglong;Lee, Bong-Jin
通讯作者：
Lee, Bong-Jin
影响因子：
15.9
作者：
Williams, Julia J.;Hergenrother, Paul J.
通讯作者：
Hergenrother, Paul J.
影响因子：
3.1
作者：
DUNN, PL;NORTH, RJ
通讯作者：
NORTH, RJ
影响因子：
2.1
作者：
Demidenok, Oksana I.;Kaprelyants, Arseny S.;Goncharenko, Anna V.
通讯作者：
Goncharenko, Anna V.