Phosphonamidate and phosphothioate dipeptides as potential inhibitors of VanX.
In an effort to prepare novel inhibitors of VanX, N-[(1-aminoethyl)hydroxyphosphinyl]-D-alanine 1 and S-[(aminoethyl)hydroxyphosphinyl]-thiolacetic acid 2 were synthesized and evaluated as inhibitors of VanX. Phosphonamidate 1 was shown to be a partial competitive inhibitor of VanX with a Ki of 36+/-3 microM, and phosphothioate 2 was shown not to inhibit VanX.
Yang
K W
KW
Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
Brandt
J J
JJ
Chatwood
L L
LL
Crowder
M W
MW
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D004151:Dipeptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D013329:Structure-Activity Relationship; D020713:Vancomycin Resistance; D065093:beta-Lactamase Inhibitors
D001426:Bacterial Proteins; D004151:Dipeptides; C413734:N-((1-aminoethyl)hydroxyphosphinyl)alanine; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D065093:beta-Lactamase Inhibitors; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C091956:VanX dipeptidase; D000409:Alanine