Thanatin and vinyl sulfide analogues as narrow spectrum antimicrobial peptides that synergise with polymyxin B.

ABSTRACT: Thanatin is a β-hairpin antimicrobial peptide cyclised by a single disulfide bond that has shown potent broad-spectrum activity towards bacterial and fungal pathogens. Towards Gram-negative species, thanatin acts both by forming trans-membranal pores and inhibiting outer membrane biogenesis by binding to LptA and blocking lipopolysaccharide (LPS) transport. Inspired by previous modifications of thanatin, an analogue was prepared which demonstrated potent but selective activity towards E. coli. Furthermore, this compound was shown to act in synergy with the highly potent FDA-approved lipopeptide antibiotic polymyxin B, which engages LPS at the cytoplasmic membrane. Four analogues of thanatin in which the disulfide was substituted for vinyl sulfide bridge mimetics were prepared, all o

SUBMITTER: Shepperson OA 

PROVIDER: S-EPMC11573584 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature