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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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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. |
format | Online Article Text |
id | pubmed-4189773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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