Abstract
Thienopyrimidine-based allosteric inhibitors of the human farnesyl pyrophosphate synthase (hFPPS), characterized by a chiral α-aminophosphonic acid moiety, were synthesized as enantiomerically enriched pairs, and their binding mode was investigated by X-ray crystallography. A general consensus in the binding orientation of all (R)- and (S)-enantiomers was revealed. This finding is a prerequisite for establishing a reliable structure-activity relationship (SAR) model.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation / drug effects
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Aminoethylphosphonic Acid / chemistry*
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Aminoethylphosphonic Acid / pharmacology*
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Humans
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Ligases / antagonists & inhibitors*
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Ligases / chemistry*
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Ligases / metabolism
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Models, Molecular
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Polyisoprenyl Phosphates / metabolism*
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Protein Conformation
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Sesquiterpenes / metabolism*
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Polyisoprenyl Phosphates
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Sesquiterpenes
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farnesyl pyrophosphate
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Aminoethylphosphonic Acid
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Ligases