Origins of cell selectivity of cationic steroid antibiotics.
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.
Ding
Bangwei
B
Contribution from the Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, USA.
Yin
Ning
N
Liu
Yang
Y
Cardenas-Garcia
Jaime
J
Evanson
Richard
R
Orsak
Thomas
T
Fan
Mingjin
M
Turin
Gracija
G
Savage
Paul B
PB
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
D000900:Anti-Bacterial Agents; D002412:Cations; D008050:Lipid A; D013256:Steroids