Search

Your search keyword '"Temple KJ"' showing total 3 results
Start Over Author "Temple KJ" Topic alkyl and aryl transferases
3 results on '"Temple KJ"'

1. Synthesis of Non-natural, Frame-Shifted Isoprenoid Diphosphate Analogues.

Author

Temple KJ, Wright EN, Fierke CA, and Gibbs RA

Subjects
Alkyl and Aryl Transferases metabolism, Diphosphates chemical synthesis, Diphosphates chemistry, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Farnesyltranstransferase metabolism, Molecular Structure, Terpenes chemical synthesis, Terpenes chemistry, Alkyl and Aryl Transferases antagonists & inhibitors, Diphosphates pharmacology, Enzyme Inhibitors pharmacology, Farnesyltranstransferase antagonists & inhibitors, Terpenes pharmacology
Abstract

A set of synthetic approaches was developed and applied to the synthesis of eight frame-shifted isoprenoid diphosphate analogues. These analogues were designed to increase or decrease the methylene units between the double bonds and/or the pyrophosphate moieties of the isoprenoid structure. Evaluation of mammalian GGTase-I and FTase revealed that small structural changes can result in substantial changes in substrate activity.

Published
2016
Full Text
View/download PDF

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

Author

Temple KJ, Wright EN, Fierke CA, and Gibbs RA

Subjects
Alkyl and Aryl Transferases metabolism, Dose-Response Relationship, Drug, Humans, Molecular Structure, Polyisoprenyl Phosphates chemistry, Structure-Activity Relationship, Alkyl and Aryl Transferases antagonists & inhibitors, Polyisoprenyl Phosphates chemical synthesis, Polyisoprenyl Phosphates pharmacology
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)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Published
2016
Full Text
View/download PDF

3. Exploration of GGTase-I substrate requirements. Part 1: Synthesis and biochemical evaluation of novel aryl-modified geranylgeranyl diphosphate analogs.

Author

Temple KJ, Wright EN, Fierke CA, and Gibbs RA

Subjects
Alkyl and Aryl Transferases metabolism, Animals, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Humans, Molecular Structure, Polyisoprenyl Phosphates chemical synthesis, Polyisoprenyl Phosphates chemistry, Structure-Activity Relationship, Alkyl and Aryl Transferases antagonists & inhibitors, Enzyme Inhibitors pharmacology, Polyisoprenyl Phosphates pharmacology
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, with 6d having a krel=1.93 when compared to GGPP (krel=1.0)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results