Structure-activity relationships of the peptide deformylase inhibitor BB-3497: modification of the metal binding group.
A series of analogues of the potent peptide deformylase (PDF) inhibitor BB-3497 containing alternative metal binding groups was synthesised. Enzyme inhibition and antibacterial activity data for these compounds revealed that the bidentate hydroxamic acid and N-formyl hydroxylamine structural motifs represent the optimum chelating groups on the pseudopeptidic BB-3497 backbone.
Smith
Helen K
HK
British Biotech Pharmaceuticals Limited, Watlington Road, Oxford OX4 6LY, UK.
Beckett
R Paul
RP
Clements
John M
JM
Doel
Sheila
S
East
Stephen P
SP
Launchbury
Steven B
SB
Pratt
Lisa M
LM
Spavold
Zoë M
ZM
Thomas
Wayne
W
Todd
Richard S
RS
Whittaker
Mark
M
D000581:Amidohydrolases; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D001419:Bacteria / Q000187:drug effects; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008670:Metals / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
C425109:BB3497; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D006877:Hydroxamic Acids; D008670:Metals; D000626:Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase