Synthesis and characterization of peptide-cationic steroid antibiotic conjugates.
[reaction: see text] New cationic steroid antibiotics have been prepared by conjugating tripeptides to a triamino analogue of cholic acid. These compounds were synthesized on a solid phase in an indexed library that was screened for antibacterial activity against Gram-negative and Gram-positive bacteria. Selected compounds were synthesized on a larger scale, and minimum inhibition concentrations were measured. These results correlated very well with the screening of the indexed library of antibiotics. The most active antibiotics demonstrate a marked improvement over a related and well characterized cationic steroid antibiotic.
Ding
Bangwei
B
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, USA.
Taotofa
Uale
U
Orsak
Thomas
T
Chadwell
Matthew
M
Savage
Paul B
PB
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002793:Cholic Acids / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002793:Cholic Acids; D009842:Oligopeptides; D013256:Steroids