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Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations

BioMed Research International. 2014;2014 DOI 10.1155/2014/389869

 

Journal Homepage

Journal Title: BioMed Research International

ISSN: 2314-6133 (Print); 2314-6141 (Online)

Publisher: Hindawi Limited

LCC Subject Category: Medicine

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML, ePUB, XML

 

AUTHORS


Pavel Mader (Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 140 00 Prague 4, Czech Republic)

Adam Pecina (Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic)

Petr Cígler (Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic)

Martin Lepšík (Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic)

Václav Šícha (Institute of Inorganic Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Hlavní 1001, 250 68 Řež near Prague, Czech Republic)

Pavel Hobza (Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic)

Bohumír Grüner (Institute of Inorganic Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Hlavní 1001, 250 68 Řež near Prague, Czech Republic)

Jindřich Fanfrlík (Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences and IOCB Research Center, Flemingovo nam. 2, 166 10 Prague 6, Czech Republic)

Jiří Brynda (Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 140 00 Prague 4, Czech Republic)

Pavlína Řezáčová (Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 140 00 Prague 4, Czech Republic)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 19 weeks

 

Abstract | Full Text

Carborane-based compounds are promising lead structures for development of inhibitors of carbonic anhydrases (CAs). Here, we report structural and computational analysis applicable to structure-based design of carborane compounds with selectivity toward the cancer-specific CAIX isoenzyme. We determined the crystal structure of CAII in complex with 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane at 1.0 Å resolution and used this structure to model the 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane interactions with CAIX. A virtual glycine scan revealed the contributions of individual residues to the energy of binding of 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane to CAII and CAIX, respectively.