Open AccessPhosphonopeptides as Antibacterial Agents: Rationale, Chemistry, and Structure-Activity Relationships
Author(s) -
Frank R. Atherton,
Michael J. Hali,
Cedric H. Hassall,
Robert Lambert,
Peter S. Ringrose
Publication year - 1979
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.15.5.677
Subject(s) - peptidoglycan , bacterial cell structure , residue (chemistry) , antibacterial activity , biochemistry , chemistry , antibacterial agent , peptide , biosynthesis , intracellular , amino acid , bacteria , cell wall , alanine , stereochemistry , in vitro , biology , enzyme , antibiotics , genetics
Peptide mimetics with C-terminal residues simulating natural amino acids have been designed as inhibitors of bacterial cell wall biosynthesis. The phosphonopeptide series consisting of variousl andd 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 wasl -1-aminoethylphosphonic acid. The in vitro antibacterial activities of representative phosphonodi- to phosphonohexapeptides were investigated. The antibacterial action of the active compounds has been 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.