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

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 determi...

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Veröffentlicht in:BioMed research international 2014-01, Vol.2014 (2014), p.1-9
Hauptverfasser: Řezáčová, Pavlína, Brynda, Jiří, Grüner, Bohumír, Hobza, Pavel, Šícha, Václav, Lepšík, Martin, Cígler, Petr, Pecina, Adam, Mader, Pavel, Fanfrlík, Jindřich
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Sprache:eng
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Zusammenfassung: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.
ISSN:2314-6133
2314-6141
DOI:10.1155/2014/389869