THE PHARMACOPHORE OF DEBROMOAPLYSIATOXIN RESPONSIBLE FOR PROTEIN-KINASE-C ACTIVATION

被引：32

作者：

KONG, FH

KISHI, Y

PEREZSALA, D

RANDO, RR

机构：

[1] HARVARD UNIV,DEPT CHEM,12 OXFORD ST,CAMBRIDGE,MA 02138

[2] HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1991年 / 88卷 / 05期

关键词：

3,4-DIHYDROXYBUTYRATES; CYCLIC ACYLGLYCEROLS; DIACYLGLYCEROLS; APLYSIATOXINS; STRUCTURAL CORRELATION;

D O I：

10.1073/pnas.88.5.1973

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Protein kinase C is physiologically activated by 1,2-diacyl-sn-glycerol in the S configuration. The enzyme is also powerfully activated by structurally diverse tumor promotors. A model has been developed that demonstrates how the various tumor promotors and diacylglycerols can all be accommodated by the same binding site of the kinase. One prediction of this model concerns the structural nature of the pharmacophore in the tumor promotor debromoaplysiatoxin. This prediction is realized by synthesizing the analogs with the deduced pharmacophore and demonstrating that they are potent activators of protein kinase C. These findings provide strong experimental support for our structural model of protein kinase C activation.

引用

页码：1973 / 1976

页数：4

共 18 条

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[2]

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[3]

CASTAGNA M, 1982, J BIOL CHEM, V257, P7847

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