Abstract

Fluorescent pteridine-based nucleoside analogs that can be site-specifically incorporated into DNA oligonucleotides through a phosphodiester linkage have been developed and patented. The fluorescence properties of a series of these compounds have been characterized and potential applications are being investigated. These new fluorophores are promising probes for the study of protein/DNA interactions, because they are not attached to DNA externally and they do not appear to disrupt the tertiary structure of DNA. Rapid fluorescence-based assays for HIV-1 integrase and alkylguanine-DNA-akyltransferase have been developed, and the utility of these fluorophores as hybridization probes has been patented and is under investigation. A number of collaborative studies investigating the potential applications of these new research tools are also underway, and the probes have been licensed by Trilink Technologies and are commercially available.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Clinical Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01SC010093-06
Application #
6948104
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
Clinical Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Schrump, David S (2009) Cytotoxicity mediated by histone deacetylase inhibitors in cancer cells: mechanisms and potential clinical implications. Clin Cancer Res 15:3947-57
Risinger, John Ian; Chandramouli, Gadisetti V R; Maxwell, G Larry et al. (2007) Global expression analysis of cancer/testis genes in uterine cancers reveals a high incidence of BORIS expression. Clin Cancer Res 13:1713-9
Kang, Y; Hong, J A; Chen, G A et al. (2007) Dynamic transcriptional regulatory complexes including BORIS, CTCF and Sp1 modulate NY-ESO-1 expression in lung cancer cells. Oncogene 26:4394-403
Ziauddin, M Firdos; Yeow, Wen-Shuz; Maxhimer, Justin B et al. (2006) Valproic acid, an antiepileptic drug with histone deacetylase inhibitory activity, potentiates the cytotoxic effect of Apo2L/TRAIL on cultured thoracic cancer cells through mitochondria-dependent caspase activation. Neoplasia 8:446-57
Yeow, W-S; Ziauddin, M F; Maxhimer, J B et al. (2006) Potentiation of the anticancer effect of valproic acid, an antiepileptic agent with histone deacetylase inhibitory activity, by the kinase inhibitor Staurosporine or its clinically relevant analogue UCN-01. Br J Cancer 94:1436-45
Lundqvist, Andreas; Abrams, Scott I; Schrump, David S et al. (2006) Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity. Cancer Res 66:7317-25
Guo, Z Sheng; Hong, Julie A; Irvine, Kari R et al. (2006) De novo induction of a cancer/testis antigen by 5-aza-2'-deoxycytidine augments adoptive immunotherapy in a murine tumor model. Cancer Res 66:1105-13
Kassis, Edmund S; Zhao, Ming; Hong, Julie A et al. (2006) Depletion of DNA methyltransferase 1 and/or DNA methyltransferase 3b mediates growth arrest and apoptosis in lung and esophageal cancer and malignant pleural mesothelioma cells. J Thorac Cardiovasc Surg 131:298-306
Schrump, David S; Fischette, Maria R; Nguyen, Dao M et al. (2006) Phase I study of decitabine-mediated gene expression in patients with cancers involving the lungs, esophagus, or pleura. Clin Cancer Res 12:5777-85
Vatolin, Sergei; Abdullaev, Ziedulla; Pack, Svetlana D et al. (2005) Conditional expression of the CTCF-paralogous transcriptional factor BORIS in normal cells results in demethylation and derepression of MAGE-A1 and reactivation of other cancer-testis genes. Cancer Res 65:7751-62

Showing the most recent 10 out of 26 publications