In vitro studies in a myelogenous leukemia cell line suggest an organized binding of geranylgeranyl diphosphate synthase inhibitors

Jacqueline E. Reilly, Xiang Zhou, Huaxiang Tong, Craig H. Kuder, David F. Wiemer, Raymond Hohl

Research output: Contribution to journalArticle

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Abstract

A small set of isoprenoid bisphosphonates ethers has been tested in the K562 chronic myelogenous leukemia cell line to determine their impact on isoprenoid biosynthesis. Five of these compounds inhibit geranylgeranyl diphosphate synthase (GGDPS) with IC50 values below 1 μM in enzyme assays, but in cells their apparent activity is more varied. In particular, the isomeric C-geranyl-O-prenyl and C-prenyl-O-geranyl bisphosphonates are quite different in their activity with the former consistently demonstrating greater impairment of geranylgeranylation in cells but the latter showing greater impact in the enzyme assays with GGDPS. Together, these findings suggest an organized binding of these inhibitors in the two hydrophobic channels of the geranylgeranyl diphosphate synthase enzyme.

Original languageEnglish (US)
Pages (from-to)83-92
Number of pages10
JournalBiochemical Pharmacology
Volume96
Issue number2
DOIs
StatePublished - Jun 11 2015

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Farnesyltranstransferase
Myeloid Leukemia
Terpenes
Cells
Diphosphonates
Enzyme Assays
Cell Line
Assays
Enzymes
Prenylation
Ethers
Biosynthesis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Inhibitory Concentration 50
In Vitro Techniques
prenyl

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Reilly, Jacqueline E. ; Zhou, Xiang ; Tong, Huaxiang ; Kuder, Craig H. ; Wiemer, David F. ; Hohl, Raymond. / In vitro studies in a myelogenous leukemia cell line suggest an organized binding of geranylgeranyl diphosphate synthase inhibitors. In: Biochemical Pharmacology. 2015 ; Vol. 96, No. 2. pp. 83-92.
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In vitro studies in a myelogenous leukemia cell line suggest an organized binding of geranylgeranyl diphosphate synthase inhibitors. / Reilly, Jacqueline E.; Zhou, Xiang; Tong, Huaxiang; Kuder, Craig H.; Wiemer, David F.; Hohl, Raymond.

In: Biochemical Pharmacology, Vol. 96, No. 2, 11.06.2015, p. 83-92.

Research output: Contribution to journalArticle

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