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Exploration of GGTase-I substrate requirements. Part 2: Synthesis and biochemical analysis of novel saturated geranylgeranyl diphosphate analogs.


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, with 11d having a krel=0.95 when compared to GGPP (krel=1.0).

SUBMITTER: Temple KJ 

PROVIDER: S-EPMC4955811 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Exploration of GGTase-I substrate requirements. Part 2: Synthesis and biochemical analysis of novel saturated geranylgeranyl diphosphate analogs.

Temple Kayla J KJ   Wright Elia N EN   Fierke Carol A CA   Gibbs Richard A RA  

Bioorganic & medicinal chemistry letters 20160615 15


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, with 11d having a krel=0.95 when comp  ...[more]

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