The most used approaches in structure-based drug design possess peculiar characteristics with advantages and limitations, and thus the management of complementary data from various techniques is of particular interest to synergistically achieve the development of effective enzyme inhibitors. In this Letter, we describe the application of experimental and computational techniques to study the interactions between human carbonic anhydrases and sulfonamide inhibitors. In particular, a series of affinity-labeled carbonic anhydrase inhibitors containing sulfonamido photoprobes was designed and synthesized, and one of these compounds, a benzophenone derivative, was chosen as a model photoprobe/inhibitor. A photoaffinity labeling method followed by mass spectrometry analysis was then applied to elucidate the inhibitor binding site, and a comparison with X-ray crystallography and molecular dynamics simulation data was carried out, highlighting that to have a comprehensive view of the protein/inhibitor complex stabilization all three kinds of experiments are necessary.

Interaction Studies between Carbonic Anhydrase and a Sulfonamide Inhibitor by Experimental and Theoretical Approaches / Pagnozzi, Daniela; Pala, Nicolino; Biosa, Grazia; Dallocchio, Roberto Nico; Dess??, Alessandro; Singh, Pankaj Kumar; Rogolino, Dominga; Di Fiore, Anna; De Simone, Giuseppina; Supuran, Claudiu T.; Sechi, Mario. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 13:2(2022), pp. 271-277. [10.1021/acsmedchemlett.1c00644]

Interaction Studies between Carbonic Anhydrase and a Sulfonamide Inhibitor by Experimental and Theoretical Approaches

Nicolino Pala;Roberto Dallocchio;Pankaj Kumar Singh;Mario Sechi
2022

Abstract

The most used approaches in structure-based drug design possess peculiar characteristics with advantages and limitations, and thus the management of complementary data from various techniques is of particular interest to synergistically achieve the development of effective enzyme inhibitors. In this Letter, we describe the application of experimental and computational techniques to study the interactions between human carbonic anhydrases and sulfonamide inhibitors. In particular, a series of affinity-labeled carbonic anhydrase inhibitors containing sulfonamido photoprobes was designed and synthesized, and one of these compounds, a benzophenone derivative, was chosen as a model photoprobe/inhibitor. A photoaffinity labeling method followed by mass spectrometry analysis was then applied to elucidate the inhibitor binding site, and a comparison with X-ray crystallography and molecular dynamics simulation data was carried out, highlighting that to have a comprehensive view of the protein/inhibitor complex stabilization all three kinds of experiments are necessary.
Interaction Studies between Carbonic Anhydrase and a Sulfonamide Inhibitor by Experimental and Theoretical Approaches / Pagnozzi, Daniela; Pala, Nicolino; Biosa, Grazia; Dallocchio, Roberto Nico; Dess??, Alessandro; Singh, Pankaj Kumar; Rogolino, Dominga; Di Fiore, Anna; De Simone, Giuseppina; Supuran, Claudiu T.; Sechi, Mario. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - 13:2(2022), pp. 271-277. [10.1021/acsmedchemlett.1c00644]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/298004
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