(1-Amino-2-propenyl)phosphonic acid, an inhibitor of alanine racemase and D-alanine:D-alanine ligase

• Published in: Journal of medicinal chemistry Vol. 29; no. 4; pp. 579 - 581
• Main Authors: Vo Quang Yen, Carniato, Denis, Vo Quang, Liliane, Lacoste, Anne Marie, Neuzil, Eugene, Le Goffic, Francois
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.04.1986
• Subjects: Alanine Racemase - antagonists & inhibitors; Alanine Transaminase - antagonists & inhibitors; Amino Acid Isomerases - antagonists & inhibitors; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Aspartate Aminotransferases - antagonists & inhibitors; Bacteria - drug effects; Chemistry; D-Amino-Acid Oxidase - antagonists & inhibitors; Exact sciences and technology; Organic chemistry; Organometalloidal and organometallic compounds; Organophosphorus Compounds - chemical synthesis; Organophosphorus Compounds - pharmacology; P derivatives; Peptide Synthases - antagonists & inhibitors; Preparations and properties; Structure-Activity Relationship; Ligase; Alanine racemase; Aliphatic compound; Aminoacid; Enzyme inhibitor; Infrared spectrum; NMR spectrum; Biological activity; Phosphorus Organic compounds
• DOI: 10.1021/jm00154a024
• ISSN: 0022-2623

DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Streptococcus faecalis and of the D-Ala:D-Ala ligase from this latter species. This molecule is ineffective against the whole bacterial cells. Unlike vinylglycine, this unsaturated phosphonate does not inhibit the following mammalian enzymes: aspartate aminotransferase, alanine aminotransferase, D-amino acid oxidase, which indicates its specificity. Thus, its incorporation in a peptide structure could induce interesting antimicrobial properties.