Synthesis and evaluation of novel enhanced gene reporter molecules

Detection of β-galactosidase activity using 19F NMR of trifluoromethylated aryl β-d-galactopyranosides

Jianxin Yu, Li Liu, Vikram D. Kodibagkar, Weina Cui, Ralph P. Mason

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Gene therapy has emerged as a promising strategy for treatment of various diseases, but there is a pressing need for the development of non-invasive reporter techniques based on appropriate molecules and imaging modalities to assay gene expression. We now report the design, synthesis, and evaluation of novel enhanced reporter molecules, which reveal lacZ gene expression: trifluoromethylated aryl β-d-galactopyranosides. A series of five molecular structures were screened in solution and with stably transfected lacZ expressing human MCF7 breast cancer cells in vitro. p-Trifluoromethyl-o- nitrophenyl β-d-galactopyranoside (PCF3ONPG) was found to exhibit valuable properties including a single 19F NMR signal, stability in aqueous solution and with wild type cells, but a chemical shift response to enzyme cleavage (Δδ = 1.14 ppm) in breast cancer cells transfected to stably express lacZ.

Original languageEnglish (US)
Pages (from-to)326-333
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number2
DOIs
StatePublished - Jan 15 2006

Fingerprint

Galactosidases
Galactose
Reporter Genes
Gene expression
Genes
Cells
Nuclear magnetic resonance
Gene therapy
Molecules
Chemical shift
Molecular structure
Breast Neoplasms
Gene Expression
Assays
Lac Operon
Molecular Structure
Imaging techniques
Genetic Therapy
Enzymes
Therapeutics

Keywords

  • β-Galactosidase
  • F NMR
  • lacZ
  • Reporter gene

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

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abstract = "Gene therapy has emerged as a promising strategy for treatment of various diseases, but there is a pressing need for the development of non-invasive reporter techniques based on appropriate molecules and imaging modalities to assay gene expression. We now report the design, synthesis, and evaluation of novel enhanced reporter molecules, which reveal lacZ gene expression: trifluoromethylated aryl β-d-galactopyranosides. A series of five molecular structures were screened in solution and with stably transfected lacZ expressing human MCF7 breast cancer cells in vitro. p-Trifluoromethyl-o- nitrophenyl β-d-galactopyranoside (PCF3ONPG) was found to exhibit valuable properties including a single 19F NMR signal, stability in aqueous solution and with wild type cells, but a chemical shift response to enzyme cleavage (Δδ = 1.14 ppm) in breast cancer cells transfected to stably express lacZ.",
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T2 - Detection of β-galactosidase activity using 19F NMR of trifluoromethylated aryl β-d-galactopyranosides

AU - Yu, Jianxin

AU - Liu, Li

AU - Kodibagkar, Vikram D.

AU - Cui, Weina

AU - Mason, Ralph P.

PY - 2006/1/15

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AB - Gene therapy has emerged as a promising strategy for treatment of various diseases, but there is a pressing need for the development of non-invasive reporter techniques based on appropriate molecules and imaging modalities to assay gene expression. We now report the design, synthesis, and evaluation of novel enhanced reporter molecules, which reveal lacZ gene expression: trifluoromethylated aryl β-d-galactopyranosides. A series of five molecular structures were screened in solution and with stably transfected lacZ expressing human MCF7 breast cancer cells in vitro. p-Trifluoromethyl-o- nitrophenyl β-d-galactopyranoside (PCF3ONPG) was found to exhibit valuable properties including a single 19F NMR signal, stability in aqueous solution and with wild type cells, but a chemical shift response to enzyme cleavage (Δδ = 1.14 ppm) in breast cancer cells transfected to stably express lacZ.

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