负责激活蛋白激酶C的脱溴海兔毒素药效基团。
The pharmacophore of debromoaplysiatoxin responsible for protein kinase C activation.
作者信息
Kong F H, Kishi Y, Perez-Sala D, Rando R R
机构信息
Department of Chemistry, Harvard University, Cambridge, MA 02138.
出版信息
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1973-6. doi: 10.1073/pnas.88.5.1973.
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.
摘要
蛋白激酶C在生理上可被S构型的1,2 - 二酰基 - sn - 甘油激活。该酶也可被结构多样的肿瘤促进剂强烈激活。已建立了一个模型，该模型展示了各种肿瘤促进剂和二酰基甘油如何都能被激酶的同一结合位点容纳。该模型的一个预测涉及肿瘤促进剂脱溴海兔毒素中药效基团的结构性质。通过合成具有推导药效基团的类似物并证明它们是蛋白激酶C的有效激活剂，这一预测得以实现。这些发现为我们的蛋白激酶C激活结构模型提供了有力的实验支持。
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