title: Encounter with unexpected collagenase-1 selective inhibitor: switchover of inhibitor binding pocket induced by fluorine atom.
abstract: Phosphonamide-based inhibitors having trifluoromethyl moiety showed highly selective inhibition against MMP-1. A possible mechanism of the selectivity of MMP-1 inhibitors through the switchover of the binding pocket was speculated by computational calculations. As a consequence of the unexpected selectivity, the specific interaction of CF3 group of the inhibitor and Arg214 in the S1' pocket of MMP-1 conducted a low binding energy.
authors.affiliation: Department of Chemistry, R&D Laboratories, Nippon Organon K.K., 1-5-90, Tomobuchi-cho, Miyakojima-ku, 534-0016, Osaka, Japan. masaaki-sawa@dainippon-pharm.co.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sawa
authors.forename: Hirosato
authors.initials: H
authors.lastname: Kondo
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Nishimura
mesh_terms: D000577:Amides / Q000737:chemistry; D001665:Binding Sites / Q000187:drug effects; D017364:Collagenases; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D005461:Fluorine / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases; D008958:Models, Molecular; D063065:Organophosphonates / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D063065:Organophosphonates; D005461:Fluorine; D017364:Collagenases; D020782:Matrix Metalloproteinases; C417249:collagenase 1