Exploration of GGTase-I substrate requirements. Part 1: Synthesis and biochemical evaluation of novel aryl-modified geranylgeranyl diphosphate analogs. Issue 15 (1st August 2016)

• Record Type: Journal Article
• Authors: Temple, Kayla J.; Wright, Elia N.; Fierke, Carol A.; Gibbs, Richard A.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 15(2016)
• Page Start: 3499
• Page End: 3502
• Publication Date: 2016-08-01
• Subjects: Geranylgeranylation -- Aryl-modified GGPP analogs -- GGTase-I -- Post-translational modification -- Protein prenylation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.06.034
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Protein geranylgeranylation is a type of post-translational modification that aids in the localization of proteins to the plasma member where they elicit cellular signals. To better understand the isoprenoid requirements of GGTase-I, a series of aryl-modified geranylgeranyl diphosphate analogs were synthesized and screened against mammalian GGTase-I. Of our seven-member library of compounds, six analogs proved to be substrates of GGTase-I, with6d having a k rel = 1.93 when compared to GGPP ( k rel = 1.0).