Accelerated discovery of novel benzodiazepine ligands by experiment-guided virtual screening

ACS Chemical Biology

Volumn 9, Issue 8, 2014, Pages 1854-1859

  Middendorp, Simon J ^a   Puthenkalam, Roshan ^b   Baur, Roland ^a   Ernst, Margot ^b   Sigel, Erwin ^a  

^a UNIVERSITY OF BERN   (Switzerland)

^b Medical University of Vienna   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; BENZODIAZEPINE; CYSTEINE; DIAZEPAM; BENZODIAZEPINE DERIVATIVE; LIGAND;

ARTICLE; BINDING AFFINITY; BINDING SITE; CHEMICAL MODIFICATION; COVALENT BOND; DRUG BINDING; DRUG STRUCTURE; HIGH THROUGHPUT SCREENING; LIGAND BINDING; MOLECULAR DOCKING; NONHUMAN; PRIORITY JOURNAL; XENOPUS; DRUG SCREENING; METABOLISM;

BENZODIAZEPINES; DRUG EVALUATION, PRECLINICAL; LIGANDS;

EID: 84906242978     PISSN: 15548929     EISSN: 15548937     Source Type: Journal    
DOI: 10.1021/cb5001873     Document Type: Article

References (29)

1. Lavecchia, A. and Di Giovanni, C. (2013) Virtual screening strategies in drug discovery: a critical review Curr. Med. Chem. 20, 2839-2860
2. Zhu, T., Cao, S., Su, P.-C., Patel, R., Shah, D., Chokshi, H. B., Szukala, R., Johnson, M. E., and Hevener, K. E. (2013) Hit identification and optimization in virtual screening: Practical recommendations based on a critical literature analysis J. Med. Chem. 56, 6560-6572
3. Olsen, R. W. and Sieghart, W. (2008) International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update Pharmacol. Rev. 60, 243-260
4. Sieghart, W. and Sperk, G. (2002) Subunit composition, distribution and function of GABAA receptor subtypes Curr. Top. Med. Chem. 2, 795-816
5. Sieghart, W. and Ernst, M. (2005) Heterogeneity of GABAA receptors: Revived interest in the development of subtype-selective drugs Curr. Med. Chem. 5, 217-242
6. Sigel, E. and Steinmann, M. E. (2012) Structure, function and modulation of GABAA receptors J. Biol. Chem. 287, 40224-40231
7. Sigel, E., Baur, R., Trube, G., Mohler, H., and Malherbe, P. (1990) The effect of subunit combination of rat brain GABAA receptors on channel function Neuron 5, 703-711
8. Minier, F. and Sigel, E. (2004) Positioning of the α-subunit isoforms confers a functional signature to γ-aminobutyric acid type A receptors Proc. Natl. Acad. Sci. U.S.A. 101, 7769-7774
9. Tretter, V., Ehya, N., Fuchs, K., and Sieghart, W. (1997) Stoichiometry and assembly of a recombinant GABAA receptor subtype J. Neurosci. 17, 2728-2737
10. Baumann, S. W., Baur, R., and Sigel, E. (2002) Forced subunit assembly in α1β2γ2 GABAA receptors. Insight into the absolute arrangement J. Biol. Chem. 277, 46020-46025
11. Baur, R., Minier, F., and Sigel, E. (2006) A GABAA receptor of defined subunit composition and positioning: concatenation of five subunits FEBS Lett. 580, 1616-1620
12. Sigel, E. and Lüscher, B. P. (2011) A closer look at the high affinity benzodiazepine binding site on GABAA receptors Curr. Top. Med. Chem. 11, 241-246
13. Richter, L., de Graaf, C., Sieghart, W., Varagic, Z., Mörzinger, M., de Esch, I. J., Ecker, G. F., and Ernst, M. (2012) Diazepam-bound GABA A receptor models identify new benzodiazepine binding-site ligands Nat. Chem. Biol. 8, 455-465
14. Foucaud, B., Perret, P., Grutter, T., and Goeldner, M. (2001) Cysteine mutants as chemical sensors for ligand-receptor interactions Trends. Pharmacol. Sci. 22, 170-173
15. Karlin, A. and Akabas, M. (1998) Substituted-cysteine accessibility method Methods Enzymol. 293, 123-145
16. Hansen, S. B., Sulzenbacher, G., Huxford, T., Marchot, P., Taylor, P., and Bourne, Y. (2005) Structures of Aplysia AChBP complexes with nicotinic agonists and antagonists reveal distinctive binding interfaces and conformations EMBO J. 24, 3635-3646
17. Dellisanti, C. D., Yao, Y., Stroud, J. C., Wang, Z., and Chen, L. (2007) Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution Nat. Neurosci. 10, 953-962
18. Hibbs, R. E. and Gouaux, E. (2011) Principles of activation and permeation in an anion-selective Cys-loop receptor Nature 474, 54-60
19. (2011) MOE (The Molecular Operating Environment), Version 2011.10, Chemical Computing Group Inc., Montreal.
20. Wolber, G. and Langer, T. (2005) LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters J. Chem. Inf. Model. 45, 160-169
21. Tang, H., Wang, X. S., Hsieh, J. H., and Tropsha, A. (2012) Do crystal structures obviate the need for theoretical models of GPCRs for structure-based virtual screening? Proteins 80, 1503-1521
22. Baur, R., Tan, K. R., Lüscher, B. P., Gonthier, A., Goeldner, M., and Sigel, E. (2008) Covalent modification of GABAA receptor isoforms by a diazepam analogue provides evidence for a novel benzodiazepine binding site that prevents modulation by these drugs J. Neurochem. 106, 2353-2363
23. Tan, K. R., Gonthier, A., Baur, R., Ernst, M., Goeldner, M., and Sigel, E. (2007) Proximity-accelerated chemical coupling reaction in the benzodiazepine binding site of GABAA receptors: superposition of different allosteric modulators J. Biol. Chem. 282, 26316-26325
24. Lüscher, B. P., Baur, R., Goeldner, M., and Sigel, E. (2012) Influence of GABAA receptor α subunit isoforms on the benzodiazepine binding site PLoS One 7, e42101
25. Berezhnoy, D., Nyfeler, Y., Gonthier, A., Schwob, H., Goeldner, M., and Sigel, E. (2004) Towards a relative orientation of benzodiazepines in their binding pocket on GABAA receptors J. Biol. Chem. 279, 3160-3168
26. Tan, K. R., Baur, R., Gonthier, A., Goeldner, M., and Sigel, E. (2007) Two neighboring residues of loop A of the α1 subunit point towards the benzodiazepine binding site of GABAA receptors FEBS Lett. 581, 4718-4722
27. Tan, K. R., Baur, R., Charon, S., Goeldner, M., and Sigel, E. (2009) Relative positioning of diazepam in the benzodiazepine binding-pocket of GABAA receptors J. Neurochem. 111, 1264-1273
28. Cheng, Y. C. and Prusoff, W. H. (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50% inhibition (I50) of an enzymatic reaction Biochem. Pharmacol. 22, 3099-3108
29. Sigel, E. and Minier, F. (2005) The Xenopus oocyte: system for the study of functional expression and modulation of proteins Mol. Nutr. Food. Res. 49, 228-234