New bivalent PKC ligands linked by a carbon spacer: Enhancement in binding affinity

Journal of Medicinal Chemistry

Volumn 46, Issue 19, 2003, Pages 4196-4204

  Sridhar, Jayalakshmi ^a   Wei, Zhi Liang ^a   Nowak, Ireneusz ^a   Lewin, Nancy E ^b   Ayres, Jolene A ^b   Pearce, Larry V ^b   Blumberg, Peter M ^b   Kozikowski, Alan P ^a  

^a GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON; LACTAM; PROTEIN KINASE C;

ALZHEIMER DISEASE; AMINO TERMINAL SEQUENCE; APOPTOSIS; ARTICLE; BINDING AFFINITY; CELL PROLIFERATION; HORMONE RELEASE; LIGAND BINDING; MITOGENESIS; PHASE SEPARATION; PROTEIN DOMAIN; SIGNAL TRANSDUCTION; TISSUE SPECIFICITY; TUMOR PROMOTION; X RAY CRYSTALLOGRAPHY;

BINDING SITES; BINDING, COMPETITIVE; CALCIUM; DIMERIZATION; DRUG DESIGN; ENZYME ACTIVATORS; HUMANS; ISOENZYMES; KINETICS; LACTAMS; LIGANDS; PROTEIN KINASE C; PROTEIN STRUCTURE, TERTIARY; PYRROLIDINONES; RADIOLIGAND ASSAY; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 0141566595     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0302041     Document Type: Article

References (41)

1. Newton, A. C. Protein Kinase C: Structure, function and regulation. J. Biol. Chem. 1995, 270, 28495-28498.
2. Quest, A. F. G. Regulation of protein kinase C: A tale of lipids and proteins. Enzyme Protein 1996, 49, 231-261.
3. Mellor, H.; Parker, P. J. The extended protein kinase C super-family. Biochem. J. 1998, 332, 281-292.
4. Ron, D.; Kazanietz, M. G. New insights into the regulation of protein kinase C and novel phorbol ester receptors. FASEB J. 2000, 13, 1658-1676.
5. Kozikowski, A. P.; Wang, S.; Ma, D.; Yao, J.; Ahmad, S.; Glazer, R. I.; Bogi, K.; Acs, P.; Modarres, S.; Lewin, N. E.; Blumberg, P. M. Modeling, chemistry, and biology of the benzolactam analogues of ILV. 2. Identification of the binding site of the benzolactams in the CRD2 activator-binding domain of PKCδ and discovery of an ILV analogue of improved isozyme selectivity. J. Med. Chem. 1997, 40, 1316-1326.
6. Irie, K.; Oie, K.; Nakahara, A.; Yanai, Y.; Ohigashi, H.; Wender, P. A.; Fukuda, H.; Konishi, H.; Kikkawa U. Molecular basis for protein kinase C isozyme selective binding: The synthesis, folding, and phorbol ester binding of cysteine-rich domains of all protein kinase C isozymes. J. Am. Chem. Soc. 1998, 120, 9159-9167.
7. Irie, K.; Nakahara, A.; Nakagawa, Y.; Ohigashi, H.; Shindo, M.; Fukuda, H.; Konishi, H.; Kikkawa, U.; Kashiwagi, K.; Saito, N. Establishment of a binding assay for protein kinase C isozymes using synthetic C1 peptides and development of new medicinal leads with protein kinase C isozyme and C1 domain selectivity. Pharmacol. Ther. 2002, 93, 271-281.
8. Hurley, J. H.; Newton, A. C.; Parker, P. J.; Blumberg, P. M.; Nishizuka, Y. Taxonomy and function of C1 protein kinase C homology domains. Protein Sci. 1997, 6, 477-480.
9. Bogi, K.; Lorenzo, P. S.; Acs, P.; Szallasi, Z.; Wagner, G. S.; Blumberg, P. M. Comparison of the roles of the C1a and C1b domains of protein kinase C alpha in ligand translocation in NIH3T3 cells. FEBS Lett. 1999, 456, 27-30.
10. Lorenzo, P. S.; Bogi, K.; Hughes, K. M.; Beheshti, M.; Battacharyya, D.; Garfield, S. H.; Petit, G. R.; Blumberg, P. M. Differential roles of the tandem C1 domains of protein kinase Cδ in the biphasic down-regulation induced by Bryostatin 1. Cancer Res. 1999, 59, 6137-6144.
11. Bogi, K.; Lorenzo, P. S.; Szallasi, Z.; Acs, P.; Wagner, G. S.; Blumberg, P. M. Differential selectivity of ligands for the C1a and C1b phorbol ester binding domains of protein kinase Cδ: possible correlation with tumor promoting activity. Cancer Res. 1998, 58, 1423-1428.
12. Slater, S. J.; Ho, C.; Kelly, M. B.; Larkin, J. D.; Taddeo, F. J.; Yeager, M. D.; Stubbs, C. D. Protein kinase C contains two activator binding sites that bind phorbol esters and diacylglycerols with opposite affinities. J. Biol. Chem. 1996, 271, 4627-4631.
13. Sheih, H. L.; Hansen, H.; Riedel, H. Activation of conventional mammalian protein kinase C isoforms expressed in budding yeast modulates the cell doubling time-a potential in vivo screen for protein kinase C activators. Cancer Detect. Prev. 1996, 20, 576-589.
14. Shieh, H. L.; Hansen, H.; Zhu, J.; Riedel, H. Differential protein kinase C ligand regulation detected in vivo by a phenotypic yeast assay. Mol. Carcinog. 1995, 12, 166-176.
15. Irie, K.; Yanai, Y.; Oie, K.; Ishizawa, J.; Nakagawa, Y.; Ohigashi, H.; Wender, P. A.; Kikkawa, U. Comparison of chemical characteristics of the first and the second cysteine-rich domains of protein kinase Cγ. Bioorg. Med. Chem. 1997, 5, 1725-1737.
16. Shirai, Y.; Segawa, S.; Kuriyama, M.; Goto, K.; Sakai, N.; Saito, N. Subtype-specific translocation of diacylglycerol kinase α and γ and its correlation with protein kinase C. J. Biol. Chem. 2000, 275, 24760-24766.
17. Stafford, M. J.; Watson, S. P.; Pears, C. J. PKD: a new protein kinase C-dependent pathway in platelets. Blood 2003, 101, 1392-1399.
18. Lint, J. V.; Rykx, A.; Vantus, T.; Vandenheede, J. Getting to know protein kinase D. Int. J. Biochem. Cell Biol. 2002, 34, 577-581.
19. Jencks, W. P. On the attribution and additivity of binding energies. Proc. Natl. Acad. Sci. U.S.A. 1981, 78, 4046-4050.
20. Kozikowski, A. P.; Nowak, I.; Petukhov, P. A.; Etcheberrigaray, R.; Mohamed, A.; Tan, M.; Levin, N.; Hennings, H.; Pearce, L. L.; Blumberg, P. M. New amide-bearing benzolactam-based PKC modulators induce enhanced secretion of the amyloid precursor protein metabolite sAPPα. J. Med. Chem. 2003, 46, 364-373.
21. Qiao, L.; Wang, S.; George, C.; Lewin, N. E.; Blumberg, P. M.; Kozikowski, A. P. Structure-based design of a new class of protein kinase C modulators. J. Am. Chem. Soc. 1998, 120, 6629-6630.
22. Qiao, L.; Zhao, L. Y.; Rong, S. B.; Wu, X. W.; Wang, S.; Fujii, T.; Karanietz, M. G.; Rauser, L.; Savage, J.; Roth, B. L.; Anderson, J. F.; Kozikowski, A. P. Rational design, synthesis and biological evaluation of rigid pyrrolidone analogues as potential inhibitors of prostate cancer cell growth. Bioorg. Med. Chem. Lett. 2001, 11, 955-959.
23. Zhang, G.; Kazanietz, M. G.; Blumberg, P. M.; Hurley, J. H. Crystal structure of the Cys2 activator-binding domain of protein kinase Cδ in complex with phorbol ester. Cell 1995, 81, 917-924.
24. Wittmann, V.; Takayama, S.; Gong, K. W.; Schmidt, G. W.; Wong, C. H. Ligand recognition by E- and P-selectin: Chemoenzymatic synthesis and inhibitory activity of bivalent sialyl Lewis x derivatives and sialyl Lewis x carboxylic acids. J. Org. Chem. 1998, 63, 5137-5143.
25. Kazanietz, M. G.; Areces, L. B.; Bahador, A.; Mischak, H.; Goodnight, J. ; Mushinski, F.; Blumberg, P. M. Characterisation of ligand and substrate specificity for the calcium-dependent and calcium-independent PKC isozymes. Mol. Pharmacol. 1993, 44, 298-307.
26. Kazanietz, M. G.; Wang, S.; Milne, G. W. A.; Lewin, N. E.; Blumberg, P. M. Residues in the second cysteine-rich region of PKC relevant to phorbol ester binding as revealed by site-directed mutagenesis. J. Biol. Chem. 1995, 270, 21852-21859.
27. Lewin, N. E.; Blumberg, P. M. [3H]phorbol 12,13-dibutyrate binding assay for protein kinase C and related proteins. In Protein Kinase C Protocols; Newton, A. C., Ed.; Humana Press: Totowa, NJ, 2003; Vol. 233, pp 12-156.
28. Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Discovering high-affinity ligands for proteins: SAR by NMR. Science 1996, 274, 1531-1541.
29. Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Discovering high-affinity ligands for proteins. Science 1997, 278, 497-503.
30. Qin, D.; Sullivan, R.; Berkowitz, W. F.; Bittman, R.; Rotenberg, S. A. inhibition of protein kinase C by dequalinium analogues: dependence on linker length and geometry. J. Med. Chem. 2000, 43, 1413-1417.
31. Zayed, S.; Sorg, B.; Hecker, E. Structure activity relations of polyfunctional diterpenes of the tigliane type, VI. Irritant and tumor promoting activities of semisynthetic mono and diesters of 12-deoxyphorbol. Planta Med. 1984, 4, 65-69.
32. Szallasi, Z.; Krsmanovic, L.; Blumberg, P. M. Nonpromoting 12-deoxyphorbol 13-esters inhibit phorbol 12-myristate 13-acetate induced tumor promotion in CD-1 mouse skin. Cancer Res. 1993, 53, 2507-2512.
33. Schmidt, R.; Hecker, E. In Carcinogenesis and Biological Effects of Tumor Promoters; Hecker, E., Füsenig, N. E., Kunz, W., Marks, F., Thielmann, H. W., Eds.; Schattauer: Stuttgart, Germany, 1982; pp 171-179.
34. Wang, Q. J.; Fang, T. W.; Fenick, D.; Garfield, S.; Bienfait, B.; Marquez, V. E.; Blumberg, P. M. The lipophilicity of phorbol esters as a critical factor in determining the pattern of translocation of protein kinase C δ fused to green fluorescent protein. J. Biol. Chem. 2000, 275, 12136-12146.
35. Basu, A.; Kozikowski, A. P.; Lazo, J. S. Structural requirements of lyngbyatoxin A for activation and downregulation of protein kinase C. Biochemistry 1992, 31, 3824-3830.
36. Kozikowski, A. P.; Shum, P. W.; Basu, A.; Lazo, J. S. Synthesis of structural analogues of lyngbyatoxin A and their evaluation as activators of protein kinase C. J. Med. Chem. 1991, 34, 2420-2430.
37. Kozikowski, A. P.; Ma, D.; Du, L.; Lewin, N. E.; Blumberg, P. M. Effect of alteration of the heterocyclic nucleus of ILV on its isoform selectivity for PKC. Palladium-catalyzed route to benzofuran analogues of ILV. J. Am. Chem. Soc. 1995, 117, 6666-6672.
38. Wada, R.; Suto, Y.; Kanai, M.; Shibasaki, M. Dramatic switching of protein kinase C agonist/antagonist activity by modifying the 12-ester side chain of phorbol esters. J. Am. Chem. Soc. 2002, 124, 10658-10659.
39. Sodeoka, M.; Arai, M. A.; Adachi, K. U.; Shibasaki, M. Rational design, synthesis, and evaluation of a new type of PKC inhibitor. J. Am. Chem. Soc. 1998, 120, 457-458.
40. Nacro, K.; Bienfait, B.; Lee, J.; Han, K. C.; Kang, J. H.; Benzaria, S.; Lewin, N. E.; Battacharyya, D. K.; Blumberg, P. M.; Marquez, V. E. Conformationally constrained analogues of diacylglycerol (DAG). 16. How much structural complexity is necessary for recognition and high binding affinity to protein kinase C? J. Med. Chem. 2000, 43, 921-944.
41. Pelter, A.; Ward, R. S.; Whalley, J. L. A facile synthesis of 2-substituted isoflavones for immunoassay: Assembly of the isoflavonoid skeleton by means of a novel cyclisation reaction. Synthesis 1998, 1793-1796.