Anthrax lethal factor protease inhibitors: synthesis, SAR, and structure-based 3D QSAR studies.
We have recently identified a series of compounds that efficiently inhibit anthrax lethal factor (LF) metallo-protease. Here we present further structure-activity relationship and CoMFA (comparative molecular field analysis) studies on newly derived inhibitors. The obtained 3D QSAR model was subsequently compared with the X-ray structure of the complex between LF and a representative compound. Our studies form the basis for the rational design of additional compounds with improved activity and selectivity.
Johnson
Sherida L
SL
Cancer Research Center and Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
Jung
Dawoon
D
Forino
Martino
M
Chen
Ya
Y
Satterthwait
Arnold
A
Rozanov
Dmitry V
DV
Strongin
Alex Y
AY
Pellecchia
Maurizio
M
D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000201:enzymology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012236:Rhodanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011480:Protease Inhibitors; C030325:anthrax toxin; D012236:Rhodanine; D008666:Metalloendopeptidases