Affinity and Selectivity of Protein-Ligand Recognition: A Minor Chemical Modification Changes Carbonic Anhydrase Binding Profile

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00638492" target="_blank" >RIV/61388963:_____/25:00638492 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1021/acs.jmedchem.5c01421" target="_blank" >https://doi.org/10.1021/acs.jmedchem.5c01421</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.5c01421" target="_blank" >10.1021/acs.jmedchem.5c01421</a>

Result language
angličtina
Original language name
Affinity and Selectivity of Protein-Ligand Recognition: A Minor Chemical Modification Changes Carbonic Anhydrase Binding Profile
Original language description
Discovery of small-molecule drugs relies on their strong binding affinity compared to nontarget proteins, thus possessing selectivity. Minor chemical structure changes usually exhibit little change in the compound efficacy, with rare exceptions. We developed a series of nearly 50 ortho-substituted benzenesulfonamides and experimentally measured their interactions with the 12 catalytically active human carbonic anhydrase (CA) isozymes. Inhibitors were designed using seven different substituent groups, including 4-sulfanyl-substituted 3-sulfamoyl benzoates and benzamides, 4-sulfinyl-substituted 3-sulfamoyl benzoates and benzamides, 4-sulfonyl-substituted 3-sulfamoyl benzoates and benzamides, and 4-amino-substituted benzamides. The oxidation state of sulfur at the ortho position significantly influenced the compound's affinity for CAIX, a target for anticancer drugs, demonstrating affinities hundreds of thousands of times stronger than related compounds. Coupled with X-ray crystal structures and molecular docking, the relationship between structure and thermodynamics offers insights into how small changes in the structure lead to significant changes in affinity for drug design.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/LX22NPO5102" target="_blank" >LX22NPO5102: National institute for cancer research</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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