-transparent.png){kind=logo}
Phospholipid-dependent, Ca2(+)-sensitive protein kinase (protein kinase C) is activated by the plant product phorbol ester at nanomolar concentrations and also in vivo at micromolar concentrations by diacylglycerols. We designed and synthesized cyclohexane diester analogues of the phorbol ester C ring as potential high-affinity activators of protein kinase C. We proposed that the necessary pharmacophore of phorbol ester could be mimicked by diesters of appropriately substituted cyclohexanediols. A series of 1,2-cyclohexanediol diesters with different substituents at position 4 was synthesized. These substituents were designed to mimic the 6,7-double bond and C-20 hydroxy of phorbol ester. Competitive binding vs [3H]phorbol dibutyrate determined that these compounds have an affinity for protein kinase C of 1 mM or more, and thus they do not bind to nor are they activators of this enzyme.
D E Kerr, and
L F Kissinger, and
M Shoyab
January 1983,
Proceedings of the National Academy of Sciences of the United States of America,
D E Kerr, and
L F Kissinger, and
M Shoyab
September 1997,
Carcinogenesis,
D E Kerr, and
L F Kissinger, and
M Shoyab
December 1986,
The Journal of biological chemistry,
D E Kerr, and
L F Kissinger, and
M Shoyab
July 1986,
FEBS letters,
D E Kerr, and
L F Kissinger, and
M Shoyab
February 1996,
Biophysical chemistry,
D E Kerr, and
L F Kissinger, and
M Shoyab
April 1989,
Biochemistry,
D E Kerr, and
L F Kissinger, and
M Shoyab
September 1991,
The Journal of biological chemistry,
D E Kerr, and
L F Kissinger, and
M Shoyab
August 1995,
Molecular pharmacology,
D E Kerr, and
L F Kissinger, and
M Shoyab
April 2005,
Biochemical and biophysical research communications,
D E Kerr, and
L F Kissinger, and
M Shoyab
April 1991,
Biochemical Society transactions,
