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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

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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Autores principales: Mader, Pavel, Pecina, Adam, Cígler, Petr, Lepšík, Martin, Šícha, Václav, Hobza, Pavel, Grüner, Bohumír, Fanfrlík, Jindřich, Brynda, Jiří, Řezáčová, Pavlína
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189773/
https://www.ncbi.nlm.nih.gov/pubmed/25309911
http://dx.doi.org/10.1155/2014/389869
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author Mader, Pavel
Pecina, Adam
Cígler, Petr
Lepšík, Martin
Šícha, Václav
Hobza, Pavel
Grüner, Bohumír
Fanfrlík, Jindřich
Brynda, Jiří
Řezáčová, Pavlína
author_facet Mader, Pavel
Pecina, Adam
Cígler, Petr
Lepšík, Martin
Šícha, Václav
Hobza, Pavel
Grüner, Bohumír
Fanfrlík, Jindřich
Brynda, Jiří
Řezáčová, Pavlína
author_sort Mader, Pavel
collection PubMed
description 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.
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spelling pubmed-41897732014-10-12 Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations Mader, Pavel Pecina, Adam Cígler, Petr Lepšík, Martin Šícha, Václav Hobza, Pavel Grüner, Bohumír Fanfrlík, Jindřich Brynda, Jiří Řezáčová, Pavlína Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2014 2014-09-18 /pmc/articles/PMC4189773/ /pubmed/25309911 http://dx.doi.org/10.1155/2014/389869 Text en Copyright © 2014 Pavel Mader et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mader, Pavel
Pecina, Adam
Cígler, Petr
Lepšík, Martin
Šícha, Václav
Hobza, Pavel
Grüner, Bohumír
Fanfrlík, Jindřich
Brynda, Jiří
Řezáčová, Pavlína
Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations
title Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations
title_full Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations
title_fullStr Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations
title_full_unstemmed Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations
title_short Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations
title_sort carborane-based carbonic anhydrase inhibitors: insight into caii/caix specificity from a high-resolution crystal structure, modeling, and quantum chemical calculations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189773/
https://www.ncbi.nlm.nih.gov/pubmed/25309911
http://dx.doi.org/10.1155/2014/389869
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