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Intrinsic Thermodynamics and Structures of 2,4- and 3,4-Substituted Fluorinated Benzenesulfonamides Binding to Carbonic Anhydrases.

Zubrienė A, Smirnov A, Dudutienė V, Timm DD, Matulienė J, Michailovienė V, Zakšauskas A, Manakova E, Gražulis S, Matulis D
ChemMedChem 12 161-176 (2017)
Related entries: 5dog, 5doh, 5e2m, 5e2n, 5ehe

Cited: 10 times
EuropePMC logo PMID: 28001003

Abstract

The goal of rational drug design is to understand structure-thermodynamics correlations in order to predict the chemical structure of a drug that would exhibit excellent affinity and selectivity for a target protein. In this study we explored the contribution of added functionalities of benzenesulfonamide inhibitors to the intrinsic binding affinity, enthalpy, and entropy for recombinant human carbonic anhydrases (CA) CA I, CA II, CA VII, CA IX, CA XII, and CA XIII. The binding enthalpies of compounds possessing similar chemical structures and affinities were found to be very different, spanning a range from -90 to +10 kJ mol-1 , and are compensated by a similar opposing entropy contribution. The intrinsic parameters of binding were determined by subtracting the linked protonation reactions. The sulfonamide group pKa values of the compounds were measured spectrophotometrically, and the protonation enthalpies were measured by isothermal titration calorimetry (ITC). Herein we describe the development of meta- or ortho-substituted fluorinated benzenesulfonamides toward the highly potent compound 10 h, which exhibits an observed dissociation constant value of 43 pm and an intrinsic dissociation constant value of 1.1 pm toward CA IX, an anticancer target that is highly overexpressed in various tumors. Fluorescence thermal shift assays, ITC, and X-ray crystallography were all applied in this work.

Articles - 5drs mentioned but not cited (2)

  1. Crystal structure correlations with the intrinsic thermodynamics of human carbonic anhydrase inhibitor binding. Smirnov A, Zubrienė A, Manakova E, Gražulis S, Matulis D. PeerJ 6 e4412 (2018)
  2. Switching the Inhibitor-Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII. Smirnovienė J, Smirnov A, Zakšauskas A, Zubrienė A, Petrauskas V, Mickevičiūtė A, Michailovienė V, Čapkauskaitė E, Manakova E, Gražulis S, Baranauskienė L, Chen WY, Ladbury JE, Matulis D. ChemistryOpen 10 567-580 (2021)


Reviews citing this publication (2)

  1. Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design. Linkuvienė V, Zubrienė A, Manakova E, Petrauskas V, Baranauskienė L, Zakšauskas A, Smirnov A, Gražulis S, Ladbury JE, Matulis D. Q Rev Biophys 51 e10 (2018)
  2. Forces Driving a Magic Bullet to Its Target: Revisiting the Role of Thermodynamics in Drug Design, Development, and Optimization. Minetti CA, Remeta DP. Life (Basel) 12 1438 (2022)

Articles citing this publication (6)

  1. Engineered Carbonic Anhydrase VI-Mimic Enzyme Switched the Structure and Affinities of Inhibitors. Kazokaitė J, Kairys V, Smirnovienė J, Smirnov A, Manakova E, Tolvanen M, Parkkila S, Matulis D. Sci Rep 9 12710 (2019)
  2. Intrinsic thermodynamics of high affinity inhibitor binding to recombinant human carbonic anhydrase IV. Mickevičiūtė A, Timm DD, Gedgaudas M, Linkuvienė V, Chen Z, Waheed A, Michailovienė V, Zubrienė A, Smirnov A, Čapkauskaitė E, Baranauskienė L, Jachno J, Revuckienė J, Manakova E, Gražulis S, Matulienė J, Di Cera E, Sly WS, Matulis D. Eur Biophys J 47 271-290 (2018)
  3. Structure and mechanism of secondary sulfonamide binding to carbonic anhydrases. Baronas D, Dudutienė V, Paketurytė V, Kairys V, Smirnov A, Juozapaitienė V, Vaškevičius A, Manakova E, Gražulis S, Zubrienė A, Matulis D. Eur Biophys J 50 993-1011 (2021)
  4. Discovery of new potent lysine specific histone demythelase-1 inhibitors (LSD-1) using structure based and ligand based molecular modelling and machine learning. Alabed SJ, Zihlif M, Taha M. RSC Adv 12 35873-35895 (2022)
  5. Exploiting activity cliffs for building pharmacophore models and comparison with other pharmacophore generation methods: sphingosine kinase 1 as case study. Mousa LA, Hatmal MM, Taha M. J Comput Aided Mol Des 36 39-62 (2022)
  6. Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells. Matulienė J, Žvinys G, Petrauskas V, Kvietkauskaitė A, Zakšauskas A, Shubin K, Zubrienė A, Baranauskienė L, Kačenauskaitė L, Kopanchuk S, Veiksina S, Paketurytė-Latvė V, Smirnovienė J, Juozapaitienė V, Mickevičiūtė A, Michailovienė V, Jachno J, Stravinskienė D, Sližienė A, Petrošiūtė A, Becker HM, Kazokaitė-Adomaitienė J, Yaromina A, Čapkauskaitė E, Rinken A, Dudutienė V, Dubois LJ, Matulis D. Sci Rep 12 17644 (2022)


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