Identification of structural-kinetic and structural-thermodynamic relationships for thrombin inhibitors

Biochemistry

Volumn 52, Issue 4, 2013, Pages 613-626

  Winquist, Johan ^a   Geschwindner, Stefan ^b   Xue, Yafeng ^b   Gustavsson, Lars ^b   Musil, Djordje ^b,c   Deinum, Johanna ^b   Danielson, U Helena ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

^c Merck Serono GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ASSOCIATION RATES; BINDING POCKETS; CHARGE REPULSION; DISSOCIATION RATES; ENTHALPY GAIN; ENZYME-INHIBITOR COMPLEX; EQUILIBRIUM DATA; H-BONDS; HYDROGEN-BOND FORMATION; HYDROPHOBIC INTERACTIONS; ISOTHERMAL MICROCALORIMETRY; LIPOPHILICITY; SIDE-CHAINS; SPR ANALYSIS; STOPPED FLOW; SURFACE PLASMON RESONANCE BIOSENSOR; THERMODYNAMIC DATA; THERMODYNAMIC EFFECT; THERMODYNAMIC PROFILES; THROMBIN INHIBITORS; THROMBIN-INHIBITOR; X RAY CRYSTAL STRUCTURES;

BIOSENSORS; CHAIN LENGTH; DIGITAL STORAGE; DISSOCIATION; ENTHALPY; ENZYME INHIBITION; HYDROGEN BONDS; KINETICS; LEAD COMPOUNDS;

SURFACE PLASMON RESONANCE;

MELAGATRAN; THROMBIN INHIBITOR;

ARTICLE; BINDING AFFINITY; BIOSENSOR; CALORIMETRY; CHEMICAL INTERACTION; CRYSTAL STRUCTURE; CRYSTALLIZATION; ENTHALPY; HYDROGEN BOND; ISOTHERMAL MICROCALORIMETRY; KINETICS; PRIORITY JOURNAL; PROTEIN STRUCTURE; SURFACE PLASMON RESONANCE; THERMODYNAMICS;

ANTITHROMBINS; AZETIDINES; BENZYLAMINES; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; DRUG DISCOVERY; HIRUDINS; HUMANS; HYDROGEN BONDING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; KINETICS; MODELS, MOLECULAR; PROTEIN BINDING; SURFACE PROPERTIES; THERMODYNAMICS; THROMBIN;

EID: 84873876347     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi301333z     Document Type: Article

References (31)

1. Copeland, R. A., Pompliano, D. L., and Meek, T. D. (2006) Drug-target residence time and its implications for lead optimization Nat. Rev. Drug Discovery 5, 730-739
2. Freire, E. (2008) Do enthalpy and entropy distinguish first in class from best in class? Drug Discovery Today 13, 869-874
3. Gallwitz, M., Enoksson, M., Thorpe, M., and Hellman, L. (2012) The extended cleavage specificity of human thrombin PLoS One 7, e31756
4. Schechter, I. and Berger, A. (1967) On the size of the active site in proteases. I. Papain Biochem. Biophys. Res. Commun. 27, 157-162
5. Elg, M., Gustafsson, D., and Deinum, J. (1997) The importance of enzyme inhibition kinetics for the effect of thrombin inhibitors in a rat model of arterial thrombosis Thromb. Haemostasis 78, 1286-1292
6. Stubbs, M. T. and Bode, W. (1993) A player of many parts: The spotlight falls on thrombin's structure Thromb. Res. 69, 1-58
7. Deinum, J., Gustavsson, L., Gyzander, E., Kullman-Magnusson, M., Edström, Å., and Karlsson, R. (2002) A Thermodynamic Characterization of the Binding of Thrombin Inhibitors to Human Thrombin, Combining Biosensor Technology, Stopped-Flow Spectrophotometry, and Microcalorimetry Anal. Biochem. 300, 152-162
8. Deinum, J., Mattsson, C., Inghardt, T., and Elg, M. (2009) Biochemical and pharmacological effects of the direct thrombin inhibitor AR-H067637 Thromb. Haemostasis 101, 1051-1059
9. Gustafsson, D., Antonsson, T., Bylund, R., Eriksson, U., Gyzander, E., Nilsson, I., Elg, M., Mattsson, C., Deinum, J., Pehrsson, S., Karlsson, O., Nilsson, A., and Sorensen, H. (1998) Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes Thromb. Haemostasis 79, 110-118
10. Nilsson, T., Sjöling-Ericksson, Å., and Deinum, J. (1998) The Mechanism of Binding of Low-Molecular-Weight Active Site Inhibitors to Human α-Thrombin J. Enzyme Inhib. Med. Chem. 13, 11-29
11. Deinum, J., Gyzander, E., and Gustavsson, L. (2003) Characterization of the interaction of α-thrombin with melagatran analogues with different P3 substituents: a kinetic and thermodynamic study. J. Thromb. Haemostasis, Abstract P0032.
12. Hanessian, S., Therrien, E., Zhang, J., Otterlo, W. v., Xue, Y., Gustafsson, D., Nilsson, I., and Fjellström, O. (2009) From natural products to achiral drug prototypes: Potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs Bioorg. Med. Chem. Lett. 19, 5429-5432
13. Nilsson, M., Hämäläinen, M., Ivarsson, M., Gottfries, J., Xue, Y., Hansson, S., Isaksson, R., and Fex, T. (2009) Compounds Binding to the S2-S3 Pockets of Thrombin J. Med. Chem. 52, 2708-2715
14. Fenton, J. W., II, Fasco, M. J., and Stackrow, A. B. (1977) Human thrombins. Production, evaluation, and properties of α-thrombin J. Biol. Chem. 252, 3587-3598
15. Dang, Q. D. and Di Cera, E. (1994) A simple activity assay for thrombin and hirudin J. Protein Chem. 13, 367-373
16. Pliska, V. and Charton, M. (1991) Antagonists as "affinity probes" for peptide hormone receptors: QSAR studies on oxytocin receptor in the rat myometrium J. Recept. Res. 11, 59-78
17. Good, N. E., Winget, G. D., Winter, W., Connolly, T. N., Izawa, S., and Singh, R. M. (1966) Hydrogen ion buffers for biological research Biochemistry 5, 467-477
18. Lottenberg, R., Hall, J. A., Blinder, M., Binder, E. P., and Jackson, C. M. (1983) The action of thrombin on peptide p-nitroanilide substrates. Substrate selectivity and examination of hydrolysis under different reaction conditions Biochim. Biophys. Acta 742, 539-557
19. Karlsson, R., Kullman-Magnusson, M., Hamalainen, M. D., Remaeus, A., Andersson, K., Borg, P., Gyzander, E., and Deinum, J. (2000) Biosensor analysis of drug-target interactions: Direct and competitive binding assays for investigation of interactions between thrombin and thrombin inhibitors Anal. Biochem. 278, 1-13
20. Karlsson, R. (1999) Affinity analysis of non-steady-state data obtained under mass transport limited conditions using BIAcore technology J. Mol. Recognit. 12, 285-292
21. Shuman, C. F., Hamalainen, M. D., and Danielson, U. H. (2004) Kinetic and thermodynamic characterization of HIV-1 protease inhibitors J. Mol. Recognit. 17, 106-119
22. Geitmann, M. and Danielson, U. H. (2007) Additional level of information about complex interaction between non-nucleoside inhibitor and HIV-1 reverse transcriptase using biosensor-based thermodynamic analysis Bioorg. Med. Chem. 15, 7344-7354
23. Cornish-Bowden, A. (2002) Enthalpy-entropy compensation: A phantom phenomenon J. Biosci. 27, 121-126
24. Dullweber, F., Stubbs, M. T., Musil, D., Sturzebecher, J., and Klebe, G. (2001) Factorising ligand affinity: A combined thermodynamic and crystallographic study of trypsin and thrombin inhibition J. Mol. Biol. 313, 593-614
25. Kabsch, W. (2010) Xds Acta Crystallogr. D66, 125-132
26. Collaborative Computational Project, Number 4 (1994) The CCP4 suite: Programs for protein crystallography Acta Crystallogr. D50, 760-763
27. Bricogne, G., Blanc, E., Brandl, M., Flensburg, C., Keller, P., Paciorek, W., Roversi, P., Smart, O. S., Vonrhein, C., and Womack, T. O. (2009) BUSTER, version 2.11.1, Global Phasing Ltd., Cambridge, United Kingdom.
28. Emsley, P. and Cowtan, K. (2004) Coot: Model-building tools for molecular graphics Acta Crystallogr. D60, 2126-2132
29. Baum, B., Mohamed, M., Zayed, M., Gerlach, C., Heine, A., Hangauer, D., and Klebe, G. (2009) More than a simple lipophilic contact: A detailed thermodynamic analysis of nonbasic residues in the s1 pocket of thrombin J. Mol. Biol. 390, 56-69
30. Biela, A., Sielaff, F., Terwesten, F., Heine, A., Steinmetzer, T., and Klebe, G. (2012) Ligand binding stepwise disrupts water network in thrombin: Enthalpic and entropic changes reveal classical hydrophobic effect J. Med. Chem. 55, 6094-6110
31. Tucker, T. J., Lumma, W. C., Mulichak, A. M., Chen, Z., Naylor-Olsen, A. M., Lewis, S. D., Lucas, R., Freidinger, R. M., and Kuo, L. C. (1997) Design of Highly Potent Noncovalent Thrombin Inhibitors That Utilize a Novel Lipophilic Binding Pocket in the Thrombin Active Site J. Med. Chem. 40, 830-832