异戊二烯化蛋白质含有与其 C 末端附近的半胱氨酸残基相连的 C 15或 C 20 类异戊二烯。在这里,我们描述了掺入二氮丙啶基团的类异戊二烯二磷酸类似物的制备,该类似物可用于探测异戊二烯化蛋白质和与其相互作用的其他蛋白质之间的相互作用。使用合成肽和完整蛋白质的研究表明,这些二氮丙啶类似物是异戊二烯基转移酶的有效底物。使用掺有二氮丙啶功能化类异戊二烯的肽进行光交联实验,选择性地与几种不同的蛋白质交联。这些新的类异戊二烯类似物应该广泛用于蛋白质异戊二烯化的研究。
Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate analogs
作者:Michelle Maynor、Sarah A. Scott、Emily L. Rickert、Richard A. Gibbs
DOI:10.1016/j.bmcl.2008.02.014
日期:2008.3
Protein prenyl transferases have been a focus of anti-cancer drug discovery in recent years due to their roles in post-translational modi. cation of small GTP binding proteins. Attention is now turning to the development of GGTase I inhibitors. Here, we present the synthesis and biological evaluation of four GGPP analogs versus mammalian GGTase I and the discovery that 7-allyl GGPP is a surprisingly efficient GGTase I substrate. (C) 2008 Elsevier Ltd. All rights reserved.