Synthesis and tumor-promoting activities of 12-epi-phorbol-12, 13-dibutyrate

被引:7
作者
Irie, K [1 ]
Nakahara, A
Ikawa, Y
Tanaka, M
Nakagawa, Y
Nakamura, Y
Ohigashi, H
Wender, PA
机构
[1] Kyoto Univ, Grad Sch Agr, Div Appl Life Sci, Kyoto 6068502, Japan
[2] Stanford Univ, Dept Chem, Stanford, CA 94305 USA
关键词
12-epi-phorbol-12,13-dibutyrate; Epstein-Barr virus; phorbol ester; protein kinase C; tumor promoter;
D O I
10.1271/bbb.64.2429
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
12-Epi-phorbol-12,13-dibutyrate (1), the C12-epimer of the most frequently used phorbol ester probe, phorbol-12,13-dibutyrate (PDBu), has been synthesized from phorbol in 9 steps in order to investigate the structural requirements for tumor-promoting activity. Compound 1 showed about 100-fold weaker in vitro biological activities related to in vivo tumor promotion, Epstein-Barr virus early antigen (EBV-EA)-inducing ability, superoxide (O-2(-)) generation-inducing ability, and binding to the protein kinase C (PKC) regulatory domain surrogate peptides. The results indicated that the beta -stereochemistry at position 12 of the phorbol skeleton is important for optimal activity. Binding selectivity to each PKC C1 domain of 1 was almost equal to that of PDBu.
引用
收藏
页码:2429 / 2436
页数:8
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