title: Anthrax lethal factor protease inhibitors: synthesis, SAR, and structure-based 3D QSAR studies.
abstract: 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.
authors.affiliation: Cancer Research Center and Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Sherida L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Dawoon
authors.initials: D
authors.lastname: Jung
authors.forename: Martino
authors.initials: M
authors.lastname: Forino
authors.forename: Ya
authors.initials: Y
authors.lastname: Chen
authors.forename: Arnold
authors.initials: A
authors.lastname: Satterthwait
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Rozanov
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Strongin
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
mesh_terms: 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
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011480:Protease Inhibitors; C030325:anthrax toxin; D012236:Rhodanine; D008666:Metalloendopeptidases