Two thioamino acids and four fiuorinated amino acids were employed to substitute either partially or entirely the Ile_(2),Ser_(3),Ile_(6),and Ser_(7) residues of Leu_(10)-teixobactin to prepare ten analogues and the b...Two thioamino acids and four fiuorinated amino acids were employed to substitute either partially or entirely the Ile_(2),Ser_(3),Ile_(6),and Ser_(7) residues of Leu_(10)-teixobactin to prepare ten analogues and the bioactivity of them was investigated.The SAR studies revealed that Ile_(6) was tolerable for both thioamidation and fiuoridation,while Ser_(7) was identified as the most tolerable site for thioamidation.Analogue 1a demonstrated comparable or slightly improved antibacterial activity,superior protease stability compared to Leu_(10)-teixobactin,while not exhibiting obvious cytotoxicity against mammalian cells.展开更多
基金supported by the National Natural Science Foundation of China(No.21977111)the Natural Science Foundation of Guangdong Province(No.2023A1515011765)Shenzhen Science and Technology Program(Nos.JCYJ20220818101404010,JCYJ20220818100412028)。
文摘Two thioamino acids and four fiuorinated amino acids were employed to substitute either partially or entirely the Ile_(2),Ser_(3),Ile_(6),and Ser_(7) residues of Leu_(10)-teixobactin to prepare ten analogues and the bioactivity of them was investigated.The SAR studies revealed that Ile_(6) was tolerable for both thioamidation and fiuoridation,while Ser_(7) was identified as the most tolerable site for thioamidation.Analogue 1a demonstrated comparable or slightly improved antibacterial activity,superior protease stability compared to Leu_(10)-teixobactin,while not exhibiting obvious cytotoxicity against mammalian cells.
