Abstract
We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Chemistry Techniques, Synthetic
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Drug Design
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Drug Evaluation, Preclinical / methods
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology*
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Glutamate Carboxypeptidase II / antagonists & inhibitors*
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Glutamate Carboxypeptidase II / chemistry
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Glutamate Carboxypeptidase II / metabolism*
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HEK293 Cells / drug effects
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Humans
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Molecular Structure
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Protein Conformation
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Structure-Activity Relationship
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Urea / chemistry*
Substances
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Enzyme Inhibitors
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Urea
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Glutamate Carboxypeptidase II