(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-17-((R)-5-(benzyloxy)-5-oxopentan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,7,12-triyl tris(2-((S)-2-amino-3-methylbutanamido)acetate)

Description

CAP 3 is a cholic acid-peptide conjugate (CAP) with antibacterial activity. It is active against the Gram-negative bacteria E. coli, K. pneumoniae, and A. baumanii (MIC₉₉s = 8, 16, and 16 μM, respectively). CAP 3 increases the fluidity of model Gram-negative bacterial membranes and binds to LPS in vitro. It reduces the biomass and number of colony-forming units in E. coli biofilms in a concentration-dependent manner. CAP 3 inhibits E. coli biofilm formation on catheters implanted in mice infected with E. coli at the incision site when applied as a coating on the catheters. CAP 3 (40 mg/kg) also reduces bacterial load in E. coli-infected wounds in mice. It is cytotoxic to A459 cells (IC₅₀ = 56.4 μM) and has hemolytic activity against human red blood cells with a 50% lysis (HC₅₀) value of 48 μM.

Uses

CAP 3 is a cholic acid-peptide conjugate (CAP) antimicrobial agent. CAP 3 effectively inhibits Gram-negative bacteria, with MIC99 (minimum inhibitory concentration for 99% bacterial killing) values of 8 μM, 16 μM, and 16 μM against E. coli, Klebsiella pneumoniae and Acinetobacter baumannii, respectively. CAP 3 exerts its antibacterial effects by disrupting the structural integrity of the bacterial lipopolysaccharide (LPS) outer membrane. CAP 3 rapidly kills bacteria, inhibits biofilm formation, and effectively combats drug-resistant strains and persistent bacterial infections[1].

References

[1] Yadav K, et al. Deciphering the Role of Intramolecular Networking in Cholic Acid-Peptide Conjugates on the Lipopolysaccharide Surface in Combating Gram-Negative Bacterial Infections. J Med Chem. 2019 Feb 28;62(4):1875-1886. DOI:10.1021/acs.jmedchem.8b01357