Title Sulfonamidinių junginių sąveikos su karboanhidrazėmis stebimųjų bei tikrinių termodinaminių ir kinetinių parametrų nustatymas /
Translation of Title Observed and intrinsic thermodynamic and kinetic parameters of sulfonamide derivative binding to carbonic anhydrases.
Authors Linkuvienė, Vaida
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Pages 40
Keywords [eng] Carbonic anhydrase ; sulfonamide ; FTSA ; ITC ; SPR
Abstract [eng] The aim of this work was to determine the influence of linked protonation effects to the thermodynamic and kinetic parameters of sulfonamide ligand binding to protein carbonic anhydrases (CA) and to explore the compound structure-thermodynamics and compound structure-kinetics relationships for the inhibitor binding to CA isoforms. Experiments provide information about all reactions that occur during complex formation. Protonation effect can influence the observed thermodynamic and kinetic parameters. However, dissection of protonation influence provides the intrinsic energies and association-dissociation rates of binding that do not depend on buffer or pH. To calculate the intrinsic parameters, the pKas of interacting species must be determined. Protonation constants of three CA isoforms and 25 benzenesulfonamides were determined. Thermodynamic parameters of CA-compound binding were obtained and the intrinsic parameters calculated. Analysis of the structure-thermodynamics relationship has been made. The protonation reaction also affects the kinetic parameters. SPR experiments of CA-sulfonamide binding were performed at different pHs and showed that the association rate constant depends on pH, while the dissociation rate constant does not. Interaction of compounds with CAs were obtained and the intrinsic parameters were calculated. Association rates of several compounds reached the diffusion-limitted rates. A model of intrinsic kinetic parameters was built.
Dissertation Institution Vilniaus universitetas.
Type Summaries of doctoral thesis
Language Lithuanian
Publication date 2017