The Pharmacophore of Debromoaplysiatoxin Responsible for Protein Kinase C Activation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1991 Mar 1

PMID 2000401

Citations 4

Authors

F H Kong

Y Kishi

D Perez-Sala

R R Rando

Affiliations

Soon will be listed here.

Abstract

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.

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