Abstract
78 kDa glucose-regulated protein (Grp78) is a heat shock protein (HSP) involved in protein folding that plays a role in cancer cell proliferation. Binding of adenosine-derived inhibitors to Grp78 was characterized by surface plasmon resonance and isothermal titration calorimetry. The most potent compounds were 13 (VER-155008) with K(D) = 80 nM and 14 with K(D) = 60 nM. X-ray crystal structures of Grp78 bound to ATP, ADPnP, and adenosine derivative 10 revealed differences in the binding site between Grp78 and homologous proteins.
MeSH terms
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Adenosine Triphosphatases / antagonists & inhibitors*
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Adenosine Triphosphatases / chemistry
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Adenosine Triphosphate / chemistry
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Adenylyl Imidodiphosphate / chemistry
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Binding Sites
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Calorimetry
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Crystallography, X-Ray
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Endoplasmic Reticulum Chaperone BiP
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Furans / chemical synthesis*
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Furans / chemistry
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HSC70 Heat-Shock Proteins / chemistry
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HSP70 Heat-Shock Proteins / chemistry
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Heat-Shock Proteins / antagonists & inhibitors*
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Heat-Shock Proteins / chemistry
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Ligands
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Models, Molecular
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Protein Binding
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Protein Conformation
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / chemistry
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Purines / chemical synthesis*
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Purines / chemistry
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Stereoisomerism
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Structure-Activity Relationship
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Surface Plasmon Resonance
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Thermodynamics
Substances
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Endoplasmic Reticulum Chaperone BiP
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Furans
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HSC70 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins
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Heat-Shock Proteins
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Ligands
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Protein Isoforms
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Purines
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Adenylyl Imidodiphosphate
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Adenosine Triphosphate
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Adenosine Triphosphatases