Gao Yangyang, Chen Huimin, Yang Weicheng, Wang Shuang, Gong Daohong, Zhang Xiao, Huang Yuanqin, Kumar Vinit, Huang Qiuqian, Kandegama W M W W, Hao Gefei
State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025, PR China.
State Key Laboratory of Green Pesticide, Central China Normal University, Wuhan 430079, PR China.
Pharmacol Res. 2024 Dec;210:107495. doi: 10.1016/j.phrs.2024.107495. Epub 2024 Nov 3.
Antibiotic resistance is a global health concern that is rapidly spreading among human and animal pathogens. Developing novel antibiotics is one of the most significant approaches to surmount antibiotic resistance. Given the difficult in identifying novel targets, cryptic binding sites provide new pockets for compounds design to combat antibiotic resistance. However, there exists a lack of comprehensive analysis and discussion on the successful utilization of cryptic pockets in overcoming antibiotic resistance. Here, we systematically analyze the crucial role of cryptic pockets in neutralizing antibiotic resistance. First, antibiotic resistance development and associated resistance mechanisms are summarized. Then, the advantages and mechanisms of cryptic pockets for overcoming antibiotic resistance were discussed. Specific cryptic pockets in resistant proteins and successful case studies of designed inhibitors are exemplified. This review provides insight into the discovery of cryptic pockets for drug design as an approach to overcome antibiotic resistance.
抗生素耐药性是一个全球健康问题，正在人类和动物病原体中迅速传播。开发新型抗生素是克服抗生素耐药性的最重要方法之一。鉴于识别新靶点存在困难，隐秘结合位点为设计对抗抗生素耐药性的化合物提供了新的口袋。然而，对于隐秘口袋在克服抗生素耐药性方面的成功利用，缺乏全面的分析和讨论。在此，我们系统地分析了隐秘口袋在中和抗生素耐药性中的关键作用。首先，总结了抗生素耐药性的发展及相关耐药机制。然后，讨论了隐秘口袋克服抗生素耐药性的优势和机制。举例说明了耐药蛋白中的特定隐秘口袋以及设计抑制剂的成功案例研究。本综述为发现用于药物设计的隐秘口袋作为克服抗生素耐药性的一种方法提供了见解。
