Synthesis of a simplified bryostatin C-ring analogue that binds to the CRD2 of human PKC-alpha and construction of a novel BC-analogue by an unusual Julia olefination process
[en] [GRAPHICS] The synthesis of two truncated bryostatin analogues 2 and 3 is described. High-field NMR measurements on the C-ring analogue 3 in (CH3CN)-H-2 containing 25% (H2O)-H-2 have shown that it binds to the CRD2 of human PKC-alpha at virtually the same position as phorbol-13-acetate (PA) and bryostatin 1 (1). NMR titration studies have also revealed that 3 binds to the CRD2 with a potency similar in magnitude to PA but much less potently than 1.
Disciplines :
Chemistry
Author, co-author :
Hale, K. J.
Frigerio, M.
Manaviazar, S.
Hummersone, M. G.
Fillingham, I. J.
Barsukov, I. G.
Damblon, Christian ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie biologique structurale
Gescher, A.
Roberts, G. C. K.
Language :
English
Title :
Synthesis of a simplified bryostatin C-ring analogue that binds to the CRD2 of human PKC-alpha and construction of a novel BC-analogue by an unusual Julia olefination process
Reviews: (a) Newton, A. C. Curr. Opin. Cell. Biol. 1997, 9, 161. (b) Nishizuka, Y. FASEB J. 1995, 9, 484. (c) Nishizuka, Y. Science 1992, 258, 607. (d) Mahoney, C. W.; Huang, K.-P. In Molecular and catalytic properties of protein kinase c in Protein Kinase C; Kuo, J. F., Ed.; Oxford University Press: New York, 1994; p 16.
Reviews: (a) Newton, A. C. Curr. Opin. Cell. Biol. 1997, 9, 161. (b) Nishizuka, Y. FASEB J. 1995, 9, 484. (c) Nishizuka, Y. Science 1992, 258, 607. (d) Mahoney, C. W.; Huang, K.-P. In Molecular and catalytic properties of protein kinase c in Protein Kinase C; Kuo, J. F., Ed.; Oxford University Press: New York, 1994; p 16.
Reviews: (a) Newton, A. C. Curr. Opin. Cell. Biol. 1997, 9, 161. (b) Nishizuka, Y. FASEB J. 1995, 9, 484. (c) Nishizuka, Y. Science 1992, 258, 607. (d) Mahoney, C. W.; Huang, K.-P. In Molecular and catalytic properties of protein kinase c in Protein Kinase C; Kuo, J. F., Ed.; Oxford University Press: New York, 1994; p 16.
Reviews: (a) Newton, A. C. Curr. Opin. Cell. Biol. 1997, 9, 161. (b) Nishizuka, Y. FASEB J. 1995, 9, 484. (c) Nishizuka, Y. Science 1992, 258, 607. (d) Mahoney, C. W.; Huang, K.-P. In Molecular and catalytic properties of protein kinase c in Protein Kinase C; Kuo, J. F., Ed.; Oxford University Press: New York, 1994; p 16.
Fields, A. P.; Pettit, G. R.; Stratford May, W. J. Biol. Chem. 1988, 263, 8253.
(a) Borner, C.; Guadagno, S. N.; Fabbro, D.; Weinstein, I. B. J. Biol. Chem. 1992, 267, 12892.
(b) Mischak, H.; Goodnight, J.; Kolch, W.; Martiny-Baron, G.; Schaechtle, C.; Kazanietz, M. G.; Blumberg, P. M.; Pierce, J.; Mushinski, J. F. J. Biol. Chem. 1993, 268, 6090.
Mischak, H.; Pierce, J. H.; Goodnight, J.; Kazanietz, M. G.; Blumberg, P. M.; Mushinski, J. F. J. Biol. Chem. 1993, 268, 20110.
Stanwell, C.; Gescher, A.; Bradshaw, T. D.; Pettit, G. R. Int. J. Cancer 1994, 56, 585.
Deacon, E. M.; Pongracz, J.; Griffiths, G.; Lord, J. M. Mol. Pathol. 1997, 50, 124.
Fukumoto, S.; Nishizawa, Y.; Hosoi, M.; Koyama, H.; Yamakawa, K.; Ohno, S.; Morii, H. J. Biol. Chem. 1997, 272, 13816.
Heit, I.; Weiser, R. J.; Herget, T.; Faust, D.; Borchert,-Stuhltrager, M.; Oesch, F.; Dietrich, C. Oncogene 2001, 20, 5143.
(a) Kraft, A. S.; Smith, J. B.; Berkow, R. L. Proc. Natl. Acad. Sci., U.S.A. 1986, 83, 1334.
(b) Jalava, A.; Lintunen, M.; Heikkila, J. Biochem. Biophys. Res. Commun. 1993, 191,472.
For reviews on bryostatin chemistry and biology, see: (a) Norcross, R.; Paterson I. Chem. Rev. 1995, 95, 2041. (b) Mutter, R.; Wills, M. Biorg. Med. Chem. 2000, 8, 1841. (c) Hale, K. J.; Hummersone, M. G.; Manaviazar, S.; Frigerio, M. Nat. Prod. Rep. 2002, 413.
For reviews on bryostatin chemistry and biology, see: (a) Norcross, R.; Paterson I. Chem. Rev. 1995, 95, 2041. (b) Mutter, R.; Wills, M. Biorg. Med. Chem. 2000, 8, 1841. (c) Hale, K. J.; Hummersone, M. G.; Manaviazar, S.; Frigerio, M. Nat. Prod. Rep. 2002, 413.
For reviews on bryostatin chemistry and biology, see: (a) Norcross, R.; Paterson I. Chem. Rev. 1995, 95, 2041. (b) Mutter, R.; Wills, M. Biorg. Med. Chem. 2000, 8, 1841. (c) Hale, K. J.; Hummersone, M. G.; Manaviazar, S.; Frigerio, M. Nat. Prod. Rep. 2002, 413.
Szallasi, Z.; Denning, M. F.; Smith, C. B.; Diugosz, A. A.; Yuspa, S. H. ; Pettit, G. R.; Blumberg, P. M. Mol. Pharmacol. 1994, 46, 840.
Zhang, G.; Kazanietz, M. G.; Blumberg, P. M.; Hurley, J. H. Cell 1995, 81, 917.
For the mechanism of PKC-α and -e degradation in human renal epithelial cells and fibroblasts, see: Lee, H.-W.; Smith, L.; Pettit, G. R.; Bingham Smith. Mol. Pharmacol. 1997, 51,439.
(a) Wender, P. A.; Hinkle, K. W.; Koehler, M. F. T.; Lippa, B. Med. Res. Rev. 1999, 19, 388.
(b) Wender, P. A.; Baryza, J. L.; Bennett, C. E.; Bi, F. C.; Brenner, S. E.; Clarke, M. O.; Horan, J. C.; Kan, C.; Lacote, E.; Lippa, B.; Nell, P. G.; Turner, T. M. J. Am. Chem. Soc. 2002, 124, 13648.
The bulk of the TPA molecule apparently serves as a hydrophobic cap for the polar inside of the CRD2. Its binding to a phosphorylated PKC favours its membrane translocation and insertion.
Hale, K. J., Frigerio, M.; Manaviazar, S. Org. Lett. 2001, 3, 3791.
(a) Ichikawa, S.; Hatanaka, H.; Takeuchi, Y. Ohno, S.; Inagaki, F. J. Biochem. 1995, 117, 566.
(b) Hommel, U.; Zurini, M.; Luytenm, M. Nature Struct. Biol. 1994, 1,383.
Groves, P.; Searle, M. S.; Waltho, J. P.; Williams, D. H. J. Am. Chem. Soc. 1995, 117, 7958.
Fillingham, I. J.; Barsukov, I. G.; Damblon, C. F.; Hale, K. J.; Frigerio, M.; Manaviazar, S.; Hummersone, M. G.; Gescher, A.; Roberts, G. C. K. Manuscript in preparation.
Hale, K. J.; Hummersone, M. G.; Bhatia, G. S. Org. Lett. 2000, 2, 2189.
Kageyama, M.; Tamura, T.; Nantz, M. H.; Roberts, J. C.; Somfai, P.; Whritenour, D. C.; Masamune, S. J. Am. Chem. Soc. 1990, 112, 7407.