Yang Tingting, Wang Yu, Ouyang Xu, Liu Yao, Li Beibei, Ba Zufang, Zhao Yuhuan, Yan Pengyi, Ren Bingqian, Yu Zhongwei, Liu Xueting, Zhong Chao, Liu Hui, Zhang Yun, Gou Sanhu, Ni Jingman
Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou 730000, P. R. China.
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 1 Xian Nong Tan Street, Beijing 100050, P. R. China.
J Med Chem. 2025 Jun 26;68(12):12573-12592. doi: 10.1021/acs.jmedchem.5c00331. Epub 2025 Jun 16.
Microbial-derived cyclic-lipid antimicrobial peptides (CLAMPs) exhibit significant toxicity, which hinders their wide application in clinical practice. However, such AMPs generally possess high antimicrobial activity and high metabolic stability. The superiority of their molecular structures merits summarization and can be utilized in the design of novel AMPs. Therefore, a heptameric CLAMP template was designed from scratch in this study, with the general formula: R-Dab-()-Tyr-[Lys---Trp---Glu]. Through modifying the -terminal acyl group and amino acids at key positions inside and outside the ring, new CLAMPs with high antimicrobial activity, low toxicity, and high stability were screened out. Among these, the newly optimized CLAMPs, and , stand out for their broad-spectrum antimicrobial efficacy, low hemolytic activity, and excellent stability. Additionally, they have good safety and antimicrobial activity . In summary, designing novel CLAMPs based on those derived from microorganisms is feasible and effective.
微生物来源的环状脂质抗菌肽（CLAMPs）具有显著毒性，这阻碍了它们在临床实践中的广泛应用。然而，这类抗菌肽通常具有高抗菌活性和高代谢稳定性。其分子结构的优势值得总结，并可用于新型抗菌肽的设计。因此，本研究从头设计了一种七聚体CLAMP模板，通式为：R-Dab-()-Tyr-[Lys---Trp---Glu]。通过修饰环内和环外关键位置的末端酰基和氨基酸，筛选出了具有高抗菌活性、低毒性和高稳定性的新型CLAMPs。其中，新优化的CLAMPs 和 因其广谱抗菌效果、低溶血活性和优异稳定性而脱颖而出。此外，它们具有良好的安全性和抗菌活性。总之，基于微生物来源的抗菌肽设计新型CLAMPs是可行且有效的。
