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.
MeSH terms
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Amides / chemistry
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Binding Sites / drug effects
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Collagenases
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Fluorine / chemistry*
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Fluorine / pharmacology
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Humans
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Matrix Metalloproteinase Inhibitors*
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Matrix Metalloproteinases
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Models, Molecular
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Organophosphonates / chemistry
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Organophosphonates / metabolism
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Protein Binding / drug effects
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Amides
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Enzyme Inhibitors
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Matrix Metalloproteinase Inhibitors
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Organophosphonates
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Fluorine
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Collagenases
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Matrix Metalloproteinases
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collagenase 1