Isobactins: O-acyl isopeptide prodrugs of teixobactin and teixobactin derivatives.

ABSTRACT: The antibiotic teixobactin is a promising drug candidate against drug-resistant pathogens, such as MRSA and VRE, but forms insoluble gels that may limit intravenous administration. O-Acyl isopeptide prodrug analogues of teixobactin circumvent the problem of gel formation while retaining antibiotic activity. The teixobactin prodrug analogues contain ester linkages between Ile₆ and Ser₇, Ile₂ and Ser₃, or between both Ile₆ and Ser₇ and Ile₂ and Ser₃. Upon exposure to physiological pH, the prodrug analogues undergo clean conversion to the corresponding amides, with half-lives between 13 and 115 min. Prodrug analogues containing lysine, arginine, or leucine at position 10 exhibit good antibiotic acti

SUBMITTER: Jones CR 

PROVIDER: S-EPMC9667932 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature