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

来源：

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY | 2000年 / 64卷 / 11期

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

页码：2429 / 2436

页数：8

共 33 条

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