Exploration of GGTase-I substrate requirements. Part 2: Synthesis and biochemical analysis of novel saturated 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: 3503
• Page End: 3507
• Publication Date: 2016-08-01
• Subjects: Protein prenylation -- Saturated GGPP analogs -- Farnesylation -- Geranylgeranylation -- Isoprenoid synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.06.035
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Protein prenylation is a type of post-translational modification that aids certain proteins in localizing to the plasma member where they activate cell signaling. To better understand the isoprenoid requirements and differences of FTase and GGTase-I, a series of saturated geranylgeranyl diphosphate analogs were synthesized and screened against both mammalian FTase and GGTase-I. Of our library of compounds, several analogs proved to be substrates of GGTase-I, with11d having a k rel = 0.95 when compared to GGPP ( k rel = 1.0).