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Carborane-containing urea-based inhibitors of glutamate carboxypeptidase II: Synthesis and structural characterization

Title
Carborane-containing urea-based inhibitors of glutamate carboxypeptidase II: Synthesis and structural characterization
Authors
Youn, S[Youn, Sihyun]Kim, KI[Kim, Kyung Im]Ptacek, J[Ptacek, Jakub]Ok, K[Ok, Kiwon]Novakova, Z[Novakova, Zora]Kim, Y[Kim, YunHye]Koo, J[Koo, JaeHyung]Barinka, C[Barinka, Cyril]Byun, Y[Byun, Youngjoo]
DGIST Authors
Koo, J[Koo, JaeHyung]
Issue Date
2015-11-15
Citation
Bioorganic and Medicinal Chemistry Letters, 25(22), 5232-5236
Type
Article
Article Type
Article
Keywords
Analogs and DerivativesAntagonists and InhibitorsBoron CompoundsBoron DerivativeCarboraneCarborane DerivativeChemistryControlled StudyCrystal StructureCrystallography, X-RayDrug SynthesisEnzyme InhibitorEnzyme InhibitorsGlutamate Carboxypeptidase IiGlutamate Carboxypeptidase Ii InhibitorHumanHumansHydrogen BondStructure AnalysisSynthesisUltrastructureUreaX-Ray Crystal StructureX Ray Crystallography
ISSN
0960-894X
Abstract
Glutamate carboxypeptidase II (GCPII) is a zinc metalloprotease on the surface of astrocytes which cleaves N-acetylaspartylglutamate to release N-acetylaspartate and glutamate. GCPII inhibitors can decrease glutamate concentration and play a protective role against apoptosis or degradation of brain neurons. Herein, we report the synthesis and structural analysis of novel carborane-based GCPII inhibitors. We determined the X-ray crystal structure of GCPII in complex with a carborane-containing inhibitor at 1.79 Å resolution. The X-ray analysis revealed that the bulky closo-carborane cluster is located in the spacious entrance funnel region of GCPII, indicating that the carborane cluster can be further structurally modified to identify promising lead structures of novel GCPII inhibitors. © 2015 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/2577
DOI
10.1016/j.bmcl.2015.09.062
Publisher
Elsevier Ltd
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesThe Koo Lab - ChemoReception Laboratory(CRLab)1. Journal Articles


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