Self-Stabilizing Covalent Ligand Targets Bacterial Phosphatidylethanolamine and Enhances Antibiotic Efficacy.

ABSTRACT: Background/Objectives: Discriminating bacterial from mammalian membranes remains a central challenge in antibiotic design. Bacterial membranes are enriched in phosphatidylethanolamine (PE), a lipid normally absent from the outer leaflet of mammalian cells, providing a signature for selective molecular engagement. We report a compact covalent ligand, 6-dimethylamino-4-ketohexanoic acid (DMAX), which targets PE via Schiff base formation, leveraging its tertiary amine to facilitate the reaction and strengthen ionic binding with the phosphate group. Methods: The reactivity of DMAX and PE was evaluated by computational simulations, and their interaction was examined by spectroscopic analyses (NMR and FT-IR) and an artificial membrane assay. The targeting ability of DMAX for live b

SUBMITTER: Masuda K 

PROVIDER: S-EPMC12845377 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature