TY - JOUR
T1 - The C4 hydroxyl group of phorbol esters is not necessary for protein kinase C binding
AU - Tanaka, Minoru
AU - Irie, Kazuhiro
AU - Nakagawa, Yu
AU - Nakamura, Yoshimasa
AU - Ohigashi, Hajime
AU - Wender, Paul A.
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research (C) (2) (No. 11660109) and on Priority Areas (A) (2) (No. 12045241) from Ministry of Education, Science, Culture and Sports of Japan (for K.I.) and from Japan Society for the Promotion of Science for Young Scientists (Y.N.), and by grants (CA31841, CA31845) from the National Institutes of Health (P.A.W.).
PY - 2001/3/12
Y1 - 2001/3/12
N2 - To investigate the role of the hydroxyl group at position 4 of the phorbol esters in protein kinase C (PKC) binding and function. 4β-deoxy-phorbol-12,13-dibutyrate (4β-deoxy-PDBu, 5a) and 4β-deoxy-phorbol-13-acetate (6a) were synthesized from phorbol (1). The binding affinities of these 4β-deoxy compounds (5a, 6a) to the 13 PKC isozyme C1 domains were quite similar to those of the corresponding 4β-hydroxy compounds (4a. 4b). suggesting that the C4 hydroxyl group of phorbol esters is not necessary for PKC binding. Moreover. functional assays showed that 4β-deoxy-PDBu (5a) exhibited biological activities (Epstein-Barr virus induction and superoxide generation) equally potent to those of PDBu (4a). These solution phase results differ from expectations based on the previously reported solid-phase structure of the complex of PKCδ-C1B and phorbol-13-acetate (4b).
AB - To investigate the role of the hydroxyl group at position 4 of the phorbol esters in protein kinase C (PKC) binding and function. 4β-deoxy-phorbol-12,13-dibutyrate (4β-deoxy-PDBu, 5a) and 4β-deoxy-phorbol-13-acetate (6a) were synthesized from phorbol (1). The binding affinities of these 4β-deoxy compounds (5a, 6a) to the 13 PKC isozyme C1 domains were quite similar to those of the corresponding 4β-hydroxy compounds (4a. 4b). suggesting that the C4 hydroxyl group of phorbol esters is not necessary for PKC binding. Moreover. functional assays showed that 4β-deoxy-PDBu (5a) exhibited biological activities (Epstein-Barr virus induction and superoxide generation) equally potent to those of PDBu (4a). These solution phase results differ from expectations based on the previously reported solid-phase structure of the complex of PKCδ-C1B and phorbol-13-acetate (4b).
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U2 - 10.1016/S0960-894X(01)00045-2
DO - 10.1016/S0960-894X(01)00045-2
M3 - Article
C2 - 11266177
AN - SCOPUS:0035848381
SN - 0960-894X
VL - 11
SP - 719
EP - 722
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 5
ER -