Phosphonopeptides as antibacterial agents: rationale, chemistry, and structure-activity relationships
Atherton, F.R.; Hall, M.J.; Hassall, C.H.; Lambert, R.W.; Ringrose, P.S.
Antimicrobial Agents and Chemotherapy 15(5): 677-683
1979
ISSN/ISBN: 0066-4804 PMID: 525986 Document Number: 153131
Peptide mimetics with C-terminal residues simulating natural amino acids were designed as inhibitors of bacterial cell wall biosynthesis. The phosphonopeptide series consisting of various L and D residues of natural amino acids combined with 1-aminoalkyl (and aryl-alkyl-) phosphonic acid residues had the most interesting antibacterial properties when the C-terminal residue was L-1-aminoethylphosphonic acid. The in vitro antibacterial activities of representative phosphonodi- to phosphonohexapeptides were investigated. The antibacterial action of the active compounds was explained in terms of transport into the bacterial cell and intracellular release of the alanine mimetic, which interferes with the biosynthesis of the peptidoglycan of the bacterial cell wall.