(beta-Chloro-alpha-aminoethyl)phosphonic acids as inhibitors of alanine racemase and D-alanine:D-alanine ligase.
The (beta-chloro-, (beta, beta-dichloro-, and (beta, beta, beta-trichloro-alpha-aminoethyl)phosphonic acids have been synthesized and their inhibitory properties on the alanine racemases [EC 5.1.1.1] and the D-Ala:D-Ala ligases [EC 6.3.2.4] from Pseudomonas aeruginosa and Streptococcus faecalis have been evaluated. The monochloro and the dichloro derivatives of Ala-P exhibit a strong inhibition on the racemases of the two species tested but do not behave as suicide substrates. Only the D-Ala:D-Ala ligase of S. faecalis is inhibited by these compounds. The poor antibacterial activity observed with beta-chloro- and beta, beta-dichloro-Ala-P might be enhanced by the peptide-transport strategy.
Vo-Quang
Y
Y
Carniato
D
D
Vo-Quang
L
L
Lacoste
A M
AM
Neuzil
E
E
Le Goffic
F
F
D000411:Alanine Racemase / Q000037:antagonists & inhibitors*; D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors*; D000615:Aminoethylphosphonic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D013293:Enterococcus faecalis / Q000201:enzymology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010453:Peptide Synthases / Q000037:antagonists & inhibitors*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D013329:Structure-Activity Relationship
D009943:Organophosphorus Compounds; D000615:Aminoethylphosphonic Acid; D000591:Amino Acid Isomerases; D000411:Alanine Racemase; D010453:Peptide Synthases; C019638:D-alanylalanine synthetase