title: Synthesis of Non-natural, Frame-Shifted Isoprenoid Diphosphate Analogues.
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.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Kayla J
authors.initials: KJ
authors.lastname: Temple
authors.affiliation: Departments of Biological Chemistry and Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Elia N
authors.initials: EN
authors.lastname: Wright
authors.affiliation: Departments of Biological Chemistry and Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Fierke
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011756:Diphosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011756:Diphosphates; D004791:Enzyme Inhibitors; D013729:Terpenes; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase