Antibacterial activity of phosphono dipeptides based on 1-amino-1-methylethanephosphonic acid.
Phosphono dipeptides containing 1-amino-1-methylethanephosphonic acid (phosphonic acid analogue of alpha-methylalanine, MeAlaP) and glycine, alanine, valine, leucine phenylalanine, proline, methionine or lysine as N- terminal component were synthesized in order to determine their antibacterial properties. Peptides containing alanine, leucine, valine phenylalanine and methionine showed marked in vitro activity, especially against Escherichia coli and Serratia marcescens strains. There were, however, generally less potent than the respective phosphono dipeptides based on 1-aminoethanephosphonic acid (phosphonic acid analogue of alanine, AlaP). The possible mechanism of action of the peptides of MeAlaP involves their active transport into the bacterial cell, followed by intracellular release of MeAlaP, which most likely inhibits alanine racemase, a key enzyme in peptidoglycan biosynthesis. Studies on the uptake of AlaMeAlaP and LeuMeAlaP by Escherichia coli mutants defective in the oligopeptide permease suggest that these peptides are not transported by the oligopeptide transport system.
Institute of Organic and Physical Chemistry, Technical University of Wrocław, Poland.
E
E
Zboińska
H
H
Sztajer
B
B
Lejczak
P
P
Kafarski
D000900:Anti-Bacterial Agents; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004058:Diffusion; D004151:Dipeptides / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates / Q000032:analysis; D009943:Organophosphorus Compounds; D012706:Serratia marcescens / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004151:Dipeptides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C065706:1-amino-1-methylethanephosphonic acid