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
- Author(s)
- Youn, Sihyun ; Kim, Kyung Im ; Ptacek, Jakub ; Ok, Kiwon ; Novakova, Zora ; Kim, YunHye ; Koo, JaeHyung ; Barinka, Cyril ; Byun, Youngjoo
- Issued Date
- 2015-11-15
- Citation
- Bioorganic and Medicinal Chemistry Letters, v.25, no.22, pp.5232 - 5236
- Type
- Article
- Author Keywords
- Carborane ; Glutamate carboxypeptidase II ; X-ray crystal structure
- Keywords
- ANALOGS ; Analogs and Derivatives ; Antagonists and Inhibitors ; Article ; BORON ; Boron Compounds ; Boron Derivative ; Carborane ; Carborane Derivative ; Chemistry ; Controlled Study ; Crystal Structure ; Crystallography, X-Ray ; DERIVATIVES ; Drug Synthesis ; EFFICACY ; Enzyme Inhibitor ; Enzyme Inhibitors ; Fluorescence ; Glutamate Carboxypeptidase II ; Glutamate Carboxypeptidase II Inhibitor ; Human ; Humans ; Hydrogen Bond ; MemBRANE ANTIGEN PSMA ; NEUTRON-CAPTURE THERAPY ; PHARMACOPHORE ; PROGESTERONE-RECEPTor ANTAGONISTS ; PROSTATE-CANCER ; Structure Analysis ; Synthesis ; Ultrastructure ; Urea ; X-Ray Crystal Structure ; X 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.
- Publisher
- Elsevier Ltd
- Related Researcher
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Koo, JaeHyung
- Research Interests 장내미생물/감염균 유래 대사체를 통한 신경염증; 알츠하이머병; 우울증; 당뇨/비만; 대사체/수용체 상호작용에 의한 대사연구
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- Appears in Collections:
- Department of New Biology Brain-Immune Axis Laboratory 1. Journal Articles
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