title: Origins of cell selectivity of cationic steroid antibiotics.
abstract: A key factor in the potential clinical utility of membrane-active antibiotics is their cell selectivity (i.e., prokaryote over eukaryote). Cationic steroid antibiotics were developed to mimic the lipid A binding character of polymyxin B and are shown to bind lipid A derivatives with affinity greater than that of polymyxin B. The outer membranes of Gram-negative bacteria are comprised primarily of lipid A, and a fluorophore-appended cationic steroid antibiotic displays very high selectivity for Gram-negative bacterial membranes over Gram-positive bacteria and eukaryotic cell membranes. This cell selectivity of cationic steroid antibiotics may be due, in part, to the affinity of these compounds for lipid A.
authors.affiliation: Contribution from the Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, USA.
authors.forename: Bangwei
authors.initials: B
authors.lastname: Ding
authors.forename: Ning
authors.initials: N
authors.lastname: Yin
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jaime
authors.initials: J
authors.lastname: Cardenas-Garcia
authors.forename: Richard
authors.initials: R
authors.lastname: Evanson
authors.forename: Thomas
authors.initials: T
authors.lastname: Orsak
authors.forename: Mingjin
authors.initials: M
authors.lastname: Fan
authors.forename: Gracija
authors.initials: G
authors.lastname: Turin
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D040761:Biomimetic Materials / Q000737:chemistry / Q000493:pharmacokinetics; D002412:Cations; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D008050:Lipid A / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000737:chemistry* / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D002412:Cations; D008050:Lipid A; D013256:Steroids