title: Design and synthesis of non-hydrolyzable homoisoprenoid α-monofluorophosphonate inhibitors of PPAPDC family integral membrane lipid phosphatases.
abstract: An efficient, diversity oriented synthesis of homoisoprenoid α-monofluorophosphonates utilizing electrophilic fluorination is presented along with their activity as inhibitors of PPAPDC2 family integral membrane lipid phosphatases. These novel phosphatase-resistant analogues of isoprenoid monophosphates are a platform for further structure-activity relationship studies and provide access to other isoprenoid family members where the phosphate ester oxygen is replaced by a α-monofluoromethylene moiety.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Thangaiah
authors.initials: T
authors.lastname: Subramanian
authors.affiliation: Division of Cardiovascular Medicine UK COM, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.affiliation: Division of Cardiovascular Medicine UK COM, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Karunai Leela
authors.initials: KL
authors.lastname: Subramanian
authors.affiliation: Division of Cardiovascular Medicine UK COM, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Manjula
authors.initials: M
authors.lastname: Sunkara
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Fredrick O
authors.initials: FO
authors.lastname: Onono
authors.affiliation: Division of Cardiovascular Medicine UK COM, University of Kentucky, Lexington, KY 40536, USA; Lexington Veterans Affairs Medical Center, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536, USA; Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA; Kentucky Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA; Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA. Electronic address: hps@uky.edu.
authors.forename: H Peter
authors.initials: HP
authors.lastname: Spielmann
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011106:Polyisoprenyl Phosphates; D010744:Phosphoric Monoester Hydrolases
keywords: Farnesyl diphosphate; Isoprenol; Mevalonate pathway; Phosphatase inhibitor; Phosphonate