Conformationally constrained analogues of diacylglycerol. 10. Ultrapotent protein kinase C ligands based on a racemic 5-disubstituted tetrahydro-2-furanone template

Journal of Medicinal Chemistry

Volumn 39, Issue 1, 1996, Pages 19-28

  Sharma, Rajiv ^a   Lee, Jeewoo ^a   Wang, Shaomeng ^a   Milne, George W A ^a   Lewin, Nancy E ^a   Blumberg, Peter M ^a   Marquez, Victor E ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4,4 BIS(HYDROXYMETHYL)TETRAHYDRO 2 FURANONE; 5 [(ACETYLOXY)METHYL] 5 (HYDROXYMETHYL) 3 (9 OCTADECENYLIDENE)TETRAHYDRO 2 FURANONE; 5 [(ACETYLOXY)METHYL] 5 (HYDROXYMETHYL) 3 TETRADECANYLIDENETETRAHYDRO 2 FURANONE; 5,5 BIS(HYDROXYMETHYL)TETRAHYDRO 2 FURANONE; DIACYLGLYCEROL; DIHYDROXYACETONE; PROTEIN KINASE C; TETRAHYDRO 2 FURANONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; DRUG CONFORMATION; DRUG STRUCTURE; ENANTIOMER; ENTROPY; RACEMIC MIXTURE; SECOND MESSENGER; STEREOSPECIFICITY;

4-BUTYROLACTONE; BINDING, COMPETITIVE; DIGLYCERIDES; DIHYDROXYACETONE; LACTONES; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; MYRISTIC ACID; MYRISTIC ACIDS; OLEIC ACID; OLEIC ACIDS; PHORBOL 12,13-DIBUTYRATE; PROTEIN KINASE C; STEREOISOMERISM;

EID: 0030050588     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950276v     Document Type: Article

References (24)

1. Lee, J.; Lewin, N. E.; Blumberg, P. M.; Marquez, V. E. Conformationally Constrained Analogues of Diacylglycerol. 9. The Effect of Side-Chain Orientation on the Protein Kinase C (PK-C) Binding Affinity of δ-Lactones. BioMed. Chem. Lett. 1994, 4, 2405-2410.
2. For a review, see: Protein Kinase C. Current Concepts and Future Perspectives; Lester, D. S., Epand, R. M., Eds.; Ellis Horwood: New York, 1992.
3. Hug, H.; Saare, T. F. Protein Kinase C Isoenzymes. Divergence in Signal Transduction. Biochem. J. 1993, 291, 329-343.
4. Leach, K. L.; James, M. L.; Blumberg, P. M. Characterization of a Specific Phorbol Ester Aporeceptor in Mouse Brain Cytosol. Proc. Natl. Acad. Sci. U.S.A 1983, 80, 4208-4212.
5. Castagna, M.; Takai, Y.; Kaibuchi, K.; Sano, K.; Kikkawa, U.; Nishizuka, Y. Direct Activation of Calcium-activated, Phospholipid-dependent Protein Kinase by Tumor-promoting Phorbol Esters. J. Biol. Chem. 1982, 257, 7847-7851.
6. Ashendel, C. L.; Staller, J. M.; Boutwell, R. K. Protein Kinase Activity Associated with a Phorbol Ester Receptor Purified from Mouse Brain. Cancer Res. 1983, 43, 4333-4337.
7. Sando, J. J.; Young, M. C. Identification of High-affinity Phorbol Ester Receptor in Cytosol of EL4 Thymoma Cells: Requirement for Calcium, Magnesium, and Phospholipids. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 2642-2646.
8. Sharkey, N. E.; Leach, K. L.; Blumberg, P. M. Competitive Inhibition by Diacylglycerol of Specific Phorbol Ester Binding. Proc. Natl. Acad. Sci. U.S.A. 1984, 81, 607-610.
9. Wilkinson, S. E.; Hallam, T. J. Protein Kinase C: Is It Pivotal Role in Cellular Activation Over-stated? Trends Pharmacol. Sci. 1994, 15, 53-57.
10. Ahmed, S.; Lee, J.; Kozma, R.; Best, A.; Monfries, C.; Lim, L. A Novel Functional Target for Tumor-promoting Phorbol Esters and Lysophosphatic Acid. J. Biol. Chem. 1993, 268, 10709-10712.
11. Teng, K.; Marquez, V. E.; Milne, G. W. A.; Barchi, J. J., Jr.; Kazanietz, M. G.; Lewin, N. E.; Blumberg, P. M.; Abushanab, E. Conformationally Constrained Analogues of Diacylglycerol. Interaction of γ-Lactones with the Phorbol Ester Receptor of Protein Kinase C. J. Am. Chem. Soc. 1992, 114, 1059-1070.
12. Wang, S.; Milne, G. W. A.; Nicklaus, M. C.; Marquez, V. E.; Lee, J.; Blumberg, P. M. Protein Kinase C. Modeling of the Binding Site and Prediction of Binding Constants. J. Med. Chem. 1994, 4, 1326-1338.
13. Lee, J.; Sharma, R.; Teng, K.; Lewin, N. E.; Blumberg, P. M.; Marquez, V. E. Conformationally Constrained Analogues of DAG. 8. Changes in PK-C Binding Affinity Produced by Isosteric Groups of the 3-O-Acyl Function in 2-Deoxy-L-Ribonolactones. BioMed. Chem. Lett. 1994, 4, 1369-1374.
14. Lee, J.; Marquez, V. E.; Lewin, N. E.; Bahador, A.; Kazanietz, M. G.; Blumberg, P. M. Conformationally Constrained Analogues of Diacylglycerol (DAG). 4. Interaction of γ-Alkylidene-γ-Lactones with Protein Kinase C (PK-C). BioMed. Chem. Lett. 1993, 3, 1107-1110.
15. Hosomi, A.; Sakurai, H. Synthesis of γ,δ-Unsaturated Alcohols from Allylsilanes and Carbonyl Compounds in the Presence of Titanium Tetrachloride. Tetrahedron Lett. 1976, 1295-1298.
16. Mandal, A. K.; Mahajan, S. W. A One-pot Synthesis of Racemic and Enantiomeric γ-Butyrolactones. Synthesis 1991, 311-313
17. Zhang, W.; Robins, M. J. Removal of Silyl Protecting Groups from Hydroxyl Functions with Ammonium Fluoride in Methnol. Tetrahedron. Lett. 1992, 33, 1177-1180.
18. Marquez, V. E.; Lee, J.; Sharma, R.; Teng, K.; Wang, S.; Lewin, N. E.; Bahador, A.; Kazanietz, M. G.; Blumberg, P. M. Conformationally Constrained Analogues of Diacylglycerol. 6. Changes in PK-C Binding Affinity for 3-O-Acyl-2-Deoxy-L-Ribonolactones Bearing Different Acyl Chains. BioMed. Chem. Lett. 1994, 4, 355-360.
19. Kazanietz, M. G.; Areres, L. B.; Bahador, A.; Mischak, H.; Goodnight, J.; Mushinski, J. F.; Blumberg, P. M. Characterization of Ligand and Substrate Specificity for the Calcium-Dependent and Calcium-Independent Protein Kinase C Isozymes. Mol. Pharmacol. 1993, 44, 298-307.
20. i) equals one, the corresponding entropic advantage for the binding of 10f at 25°C is 5.70 kJ/mol or 1.36 kcal/mol. For additional details, see ref 12.
21. Rando, R. R.; Young, N. The Stereospecific Activation of Protein. Kinase C. Biochem. Biophys. Res. Commun. 1984, 122, 818-823.
22. Allen, F. H.; Bellard, S.; Brice, M. D.; Cartwright, B. A.; Doubleday, A.; Higgs, H.; Hummelink, T.; Hummelink-Peters, B. G.; Kennard, O.; Motherwell, W. D. S.; Rodgers, J. R.; Watson, D. G. Acta Crystallogr. 1979, B35, 905. Structures with core template I: BAHREH, PERBGUY, SOFFIC, and VEFFUH. Structures with core template II: PARBUG, SIVVAU, and VEKZUG.
23. Zhang, G. G.; Kazanietz, M. G.; Blumberg, P. M.; Hurley, J. H. Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester. Cell 1995, 81, 917-924.
24. Kinder, F. R.; Tang, Y. S.; Sunay, U. B. Synthesis of Carbon-14 and Tritium Analogues of the Phospholipid Antitumor Agent SDZ 62-834zi. J. Labelled Compd. Radiopharm. 1992, 31, 829-835.