Structure-Activity Relationship of the Diaminobutyric Acid Residues in Polymyxins.

ABSTRACT: Multidrug-resistant Gram-negative bacteria have caused a serious threat to global health, and polymyxins are an important last-line therapy. As resistance to polymyxins is emerging, understanding the structure-activity relationship (SAR) of the polymyxins can facilitate the discovery of novel antimicrobial lipopeptides with improved antibacterial activity. However, l-2,4-diaminobutyric acid (Dab) is a key amino acid for the antibacterial activity of polymyxins, and the SAR of five Dab residues has not been well studied. Here, we employed an all-atom molecular dynamics simulation approach by integrating a lipidomics-informed outer membrane (OM)-based model and systematically investigated the SAR of the five Dab residues, specifically the length of their side chains. The impact of the length

SUBMITTER: Ma W 

PROVIDER: S-EPMC12569703 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature