Ding, B.; Yin, N.; Liu, Y.; Cardenas-Garcia, J.; Evanson, R.; Orsak, R.; Fan, M.; Turin, G.; Savage, P. B. J. Am. Chem. Soc. 2004, 126, 13642-13648. 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.