化学
双环分子
抗菌剂
阳离子聚合
体内
肽
抗菌肽
赖氨酸
抗生素
抗菌剂
微生物学
生物化学
立体化学
氨基酸
生物
有机化学
生物技术
作者
Tong He,Lei Xu,Yuchen Hu,Xiaomin Tang,Rui Qu,Xuejun Zhao,Hao Bai,Lixian Li,Wanyi Chen,Guangli Luo,Gang Fu,Wei Wang,Xuefeng Xia,Jinqiang Zhang
标识
DOI:10.1021/acs.jmedchem.2c00661
摘要
Antimicrobial peptides (AMPs) have attracted great attention as next generation antibiotics for the treatment of multidrug-resistant (MDR) bacterial infections. Poor proteolytic stability has however undermined clinical applications of AMPs. A novel peptide cyclization approach is described to enhance the in vivo antibacterial activity of AMPs. Bicyclic antimicrobial peptides were synthesized by cross-linking the ε-amino groups of three lysine residues with a 1,3,5-trimethylene benzene spacer. In a proof of principal study, four bicyclic peptides were synthesized from the cationic AMP OH-CM6. One bicyclic peptide retained strong antimicrobial activity and low toxicity but exhibited a prolonged half-life in serum. Antibacterial activity was consequently improved in vivo without renal or hepato-toxicity. The novel peptide cyclization approach represents an important tool for enhancing AMP proteolytic stability for improved treatment of bacterial infection.
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