Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations. (18th September 2014)

• Record Type: Journal Article
• Authors: Mader, Pavel; Pecina, Adam; Cígler, Petr; Lepšík, Martin; Šícha, Václav; Hobza, Pavel; Grüner, Bohumír; Fanfrlík, Jindřich; Brynda, Jiří; Řezáčová, Pavlína
• Other Names: Al-Rashida Mariya Academic Editor.
• Is Part Of: BioMed research international. Volume 2014(2014)
• Publication Date: 2014-09-18
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2014/389869
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : 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.