CoMFA analyses of C-2 position Salvinorin A analogs at the kappa-opioid receptor provides insights into epimer selectivity

Journal of Molecular Graphics and Modelling

Volumn 28, Issue 7, 2010, Pages 612-625

  McGovern, Donna L ^a   Mosier, Philip D ^a   Roth, Bryan L ^b   Westkaemper, Richard B ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Comparative Molecular Field Analysis (CoMFA); G protein coupled receptor (GPCR); Kappa opioid (KOP) receptor; Quantitative structure activity relationship (QSAR); Salvinorin A; Structure affinity relationship (SAFIR)

Indexed keywords

ALIGNMENT ALGORITHMS; BINDING ASSAYS; BINDING MODES; COMPARATIVE MOLECULAR FIELD ANALYSIS; CONTOUR MAP; DATA SETS; DOCKING ALGORITHMS; EPIMERS; G-PROTEIN COUPLED RECEPTORS; INTERACTION MODEL; OPIOID RECEPTORS; PREDICTIVE MODELS; PROTONATED AMINE; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS; QUANTITATIVE STRUCTURES; RADIOLIGANDS; RECEPTOR MODEL; SALVINORIN A; STRUCTURE-BASED;

ALIGNMENT; BINDING ENERGY; ORGANIC COMPOUNDS; PROTEINS; RIGID STRUCTURES; SULFUR COMPOUNDS;

THREE DIMENSIONAL;

KAPPA OPIATE RECEPTOR; SALVINORIN A;

ARTICLE; BINDING AFFINITY; COMPARATIVE MOLECULAR FIELD ANALYSIS; CONTROLLED STUDY; EPIMER; HYDROGEN BOND; HYDROPHOBICITY; NONHUMAN; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RECEPTOR BINDING;

CARBON; DIPRENORPHINE; DITERPENES, CLERODANE; HUMANS; LINEAR MODELS; MODELS, MOLECULAR; PROPYLAMINES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RECEPTORS, OPIOID, KAPPA; STEREOISOMERISM;

EID: 76549096825     PISSN: 10933263     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmgm.2009.12.008     Document Type: Article

References (48)

1. Roth B.L., Baner K., Westkaemper R.B., Siebert D., Rice K.C., Steinberg S., Ernsberger P., and Rothman R.B. Salvinorin A: a potent naturally occurring nonnitrogenous κ opioid selective agonist. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 11934-11939
2. Ortega A., Blount J.F., and Manchand P.S. Salvinorin, a New trans-Neoclerodane Diterpene from Salvia divinorum (Labiatae). J. Chem. Soc. Perkins Trans. 1 (1982) 2505-2508
3. Valdes III L.J., Butler W.M., Hatfield G.M., Paul A.G., and Koreeda M. Divinorin A, a Psychotropic Terpenoid, and Divinorin B from the Hallucinogenic Mexican Mint Salvia Divinorum. J. Org. Chem. 49 (1984) 4716-4720
4. C. Beguin, W.A. Carlezon Jr., B.M. Cohen, M. He, D.Y.-W. Lee, M.R. Richards, Salvinorin derivatives and uses thereof, WO 2005/089745, 2005.
5. C. Beguin, W.A. Carlezon Jr., B.M. Cohen, M. He, D.Y.-W. Lee, M.R. Richards, L.-Y. Liu-Chen, Salvinorin derivatives and uses thereof, US2007/0213394, 2007.
6. Béguin C., Potter D.N., DiNieri J.A., Munro T.A., Richards M.R., Paine T.A., Berry L., Zhao Z., Roth B.L., Xu W., Liu-Chen L.-Y., Carlezon Jr. W.A., and Cohen B.M. N-Methylacetamide analog of Salvinorin A: a highly potent and selective κ-opioid receptor agonist with oral efficacy. J. Pharmacol. Exp. Ther. 324 (2008) 188-195
7. Béguin C., Richards M.R., Li J.-G., Wang Y., Xu W., Liu-Chen L.-Y., Carlezon Jr. W.A., and Cohen B.M. Synthesis and in vitro evaluation of Salvinorin A analogues: effect of configuration at C(2) and substitution at C(18). Bioorg. Med. Chem. Lett. 16 (2006) 4679-4685
8. Béguin C., Richards M.R., Wang Y., Chen Y., Liu-Chen L.-Y., Ma Z., Lee D.Y.W., Carlezon Jr. W.A., and Cohen B.M. Synthesis and in vitro pharmacological evaluation of Salvinorin A analogues modified at C(2). Bioorg. Med. Chem. Lett. 15 (2005) 2761-2765
9. Bikbulatov R.V., Yan F., Roth B.L., and Zjawiony J.K. Convenient synthesis and in vitro pharmacological activity of 2-thioanalogs of Salvinorins A and B. Bioorg. Med. Chem. Lett. 17 (2007) 2229-2232
10. Chavkin C., Sud S., Jin W., Stewart J., Zjawiony J.K., Siebert D., Toth B.A., Hufeisen S.J., and Roth B.L. Salvinorin A, an active component of the hallucinogenic sage Salvia Divinorum is a highly efficacious κ-opioid receptor agonist: structural and functional considerations. J. Pharmacol. Exp. Ther. 308 (2004) 1197-1203
11. Harding W.W., Tidgewell K., Byrd N., Cobb H., Dersch C.M., Butelman E.R., Rothman R.B., and Prisinzano T.E. Neoclerodane diterpenes as a novel scaffold for μ opioid receptor ligands. J. Med. Chem. 48 (2005) 4765-4771
12. Lee D.Y.W., Karnati V.V.R., He M., Liu-Chen L.-Y., Kondaveti L., Ma Z., Wang Y., Chen Y., Beguin C., Carlezon Jr. W.A., and Cohen B. Synthesis and in vitro pharmacological studies of new C(2) modified Salvinorin A analogues. Bioorg. Med. Chem. Lett. 15 (2005) 3744-3747
13. Munro T.A., Duncan K.K., Staples R.J., Xu W., Liu-Chen L.-Y., Béguin C., Carlezon Jr. W.A., and Cohen B.M. 8-epi-Salvinorin B: crystal structure and affinity at the κ opioid receptor Beilstein. J. Org. Chem. 3 (2007) 1
14. Munro T.A., Duncan K.K., Xu W., Wang Y., Liu-Chen L.-Y., Carlezon Jr. W.A., Cohen B.M., and Béguin C. Standard protecting groups create potent and selective κ opioids: Salvinorin B alkoxymethyl ethers. Bioorg. Med. Chem. 16 (2008) 1279-1286
15. T. Prisinzano, Opioid Receptor Ligands and Methods for their Preparation, US2006/0058264, 2006.
16. Stewart D.J., Fahmy H., Roth B.L., Yan F., and Zjawiony J.K. Bioisosteric modification of Salvinorin A, a potent and selective kappa-opioid receptor agonist. Arzneimittelforschung 56 (2006) 269-275
17. Tidgewell K., Groer C.E., Harding W.W., Lozama A., Schmidt M., Marquam A., Heimstra J., Partilla J.S., Dersch C.M., Rothman R.B., Bohn L.M., and Prisinzano T.E. Herkinorin analogues with differential β-arrestin-2 interactions. J. Med. Chem. 51 (2008) 2421-2431
18. Tidgewell K., Harding W.W., Lozama A., Cobb H., Shah K., Kannan P., Dersch C.M., Parrish D., Deschamps J.R., Rothman R.B., and Prisinzano T.E. Synthesis of Salvinorin A analogs as opioid receptor probes. J. Nat. Prod. 69 (2006) 914-918
19. J.K. Zjawiony, H. Fahmy, D.J. Stewart, B.L. Roth, Agents with Selective Kappa-Opioid Receptor Affinity, WO 2006/012643, 2006.
20. Lee D.Y.W., He M., Kondaveti L., Liu-Chen L.-Y., Ma Z., Wang Y., Chen Y., Li J.-G., Beguin C., Carlezon Jr. W.A., and Cohen B. Synthesis and in vitro pharmacological studies of C(4) modified Salvinorin A analogues. Bioorg. Med. Chem. Lett. 15 (2005) 4169-4173
21. Lee D.Y.W., He M., Liu-Chen L.-Y., Wang Y., Li J.-G., Xu W., Ma Z., Carlezon Jr. W.A., and Cohen B. Synthesis and in vitro pharmacological studies of new C(4) modified Salvinorin A analogues. Bioorg. Med. Chem. Lett. 16 (2006) 5498-5502
22. Harding W.W., Schmidt M., Tidgewell K., Kannan P., Holden K.G., Dersch C.M., Rothman R.B., and Prisinzano T.E. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: selective modification of the furan ring. Bioorg. Med. Chem. Lett. 16 (2006) 3170-3174
23. Simpson D.S., Katavic P.L., Lozama A., Harding W.W., Parrish D., Deschamps J.R., Dersch C.M., Partilla J.S., Rothman R.B., Navarro H., and Prisinzano T.E. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: preparation and opioid receptor activity of salvinicin analogues. J. Med. Chem. 50 (2007) 3596-3603
24. Yan F., Mosier P.D., Westkaemper R.B., and Roth B.L. Ga-subunits differentially alter the conformation and agonist affinity of κ-opioid receptors. Biochemistry 47 (2008) 1567-1578
25. Singh N., Cheve G., Ferguson D.M., and McCurdy C.R. A combined ligand-based and target-based drug design approach for g-protein coupled receptors: application to Salvinorin A, a selective kappa opioid receptor agonist. J. Comput. Aided Mol. Des. 20 (2006) 471-493
26. Pandit D., Harding W.W., Tidgewell K., Schmidt M., Lozama A., Dersch C.M., Skawinski W.J., Rothman R.B., Prisinzano T.E., and Venanzi C.A. 233rd ACS National Meeting. Chicago, IL (2006)
27. Cramer III R.D., Patterson D.E., and Bunce J.D. Comparative molecular field analysis (CoMFA). 1: effect of shape on binding of steroids to carrier proteins. J. Am. Chem. Soc. 110 (1988) 5959-5967
28. Vortherms T., Mosier P.D., Westkaemper R.B., and Roth B.L. Differential helical orientations among related G protein-coupled receptors provide a novel mechanism for selectivity: studies with Salvinorin A and the κ-opioid receptor. J. Biol. Chem. 282 (2007) 3146-3156
29. Yan F., Mosier P.D., Westkaemper R.B., Stewart J., Zjawiony J.K., Vortherms T., Sheffler D.J., and Roth B.L. Identification of the molecular mechanisms by which the diterpenoid Salvinorin A binds to κ-opioid receptors. Biochemistry 44 (2005) 8643-8651
30. Lemmen C., Lengauer T., and Klebe G. FlexS: A method for fast flexible ligand superpositions. J. Med. Chem. 41 (1998) 4502-4520
31. Hjorth S.A., Thirstrup K., and Schwartz T.W. Radioligand-dependent discrepancy in agonist affinities enhanced by mutations in the κ-opioid receptor. Mol. Pharmacol. 50 (1996) 977-984
32. Rosenkilde M.M., Cahir M., Gether U., Hjorth S.A., and Schwartz T.W. Mutations along Transmembrane Segment II of the NK-1 receptor affect substance P competition with non-peptide antagonists but not substance P binding. J. Biol. Chem. 269 (1994) 28160-28164
33. Law P.Y., McGinn T.M., Wick M.J., Erikson L.J., Evans C., and Loh H.H. Analysis of Delta-opioid receptor activities stably expressed in CHO cell lines: function of receptor density?. J. Pharmacol. Exp. Ther. 271 (1994) 1686-1694
34. Ballesteros J.A., and Weinstein H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relationships in G-protein coupled receptors. Methods Neurosci. 25 (1995) 366-428
35. Xhaard H., Nyrönen T., Rantanen V.-V., Ruuskanen J.O., Laurila J., Salminen T., Scheinin M., and Johnson M.S. Model structures of α-2 adrenoreceptors in complex with automatically docked antagonist ligands raise the possibility of interactions dissimilar from agonist ligands. J. Struct. Biol. 150 (2005) 126-143
36. 2-guided region selection for comparative molecular field analysis: a simple method to achieve consistent results. J. Med. Chem. 38 (1995) 1060-1066
37. Kane B.E., Nieto M.J., McCurdy C.R., and Ferguson D.M. A unique binding epitope for Salvinorin A, a non-nitrogenous kappa opioid receptor agonist. FEBS J. 273 (2006) 1966-1974
38. Kane B.E., McCurdy C.R., and Ferguson D.M. Toward a structure-based model of Salvinorin A recognition of the κ-opioid receptor. J. Med. Chem. 51 (2008) 1824-1830
39. Yan F., Bikbulatov R.V., Mocanu V., Dicheva N., Parker C.E., Wetsel W.C., Mosier P.D., Westkaemper R.B., Allen J.A., Zjawiony J.K., and Roth B.L. Structure-based design, synthesis, and biochemical and pharmacological characterization of novel Salvinorin A analogues as active state probes of the κ-opioid receptor. Biochemistry 48 (2009) 6898-6908
40. Salom D., Lodowski D.T., Stenkamp R.E., Le Trong I., Golczak M., Jastrzebska B., Harris T., Ballesteros J.A., and Palczewski K. Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 16123-16128
41. de Graaf C., Foata N., Engkvist O., and Rognan D. Molecular modeling of the second extracellular loop of G-protein coupled receptors and its implication on structure-based virtual screening. Proteins 71 (2008) 599-620
42. Mobarec J.C., Sanchez R., and Filizola M. Modern homology modeling of G-protein coupled receptors: which structural template to use?. J. Med. Chem. 52 (2009) 5209-5216
43. Clark R.D. A ligand's-eye view of protein binding. J. Comput. Aided Mol. Des. 22 (2008) 507-521
44. 2 adrenoceptor binding site with catechol reveals differences in binding and activation by agonists and partial agonists. J. Biol. Chem. 280 (2005) 22165-22171
45. 2 adrenoceptor: kinetic evidence for intermediate conformational states. J. Biol. Chem. 279 (2004) 686-691
46. Kenakin T. Functional selectivity through protean and biased agonism: who steers the ship?. Mol. Pharmacol. 72 (2007) 1393-1401
47. Nygaard R., Frimurer T.M., Holst B., Rosenkilde M.M., and Schwartz T.W. Ligand binding and micro-switches in 7TM receptor structures. Trends Pharmacol. Sci. 30 (2009) 249-259
48. Lee D.Y.W., Ma Z., Liu-Chen L.-Y., Wang Y., Chen Y., Carlezon Jr. W.A., and Cohen B. New neoclerodane diterpenoids isolated from the leaves of Salvia divinorum and their binding affinities for human κ opioid receptors. Bioorg. Med. Chem. 13 (2005) 5635-5639