Abstract

) The goal of the NCDDG is to develop a cancer treatment strategy based on the selective expression of a unique purine cleavage enzyme in tumor cells. The Biochemistry Program has 3 main objectives: The first is to verify and quantitate expression of enzymes delivered to tumors cells in vitro and in vivo by a variety of mechanisms in support of the gene delivery and in vivo efficacy studies; the second objective is to characterize the substrate characteristics of new purine cleavage enzymes to aid in the development of improved enzyme/prodrug combinations; and the third objective is to perform experiments to increase the basic understanding of the biochemical pharmacology involved with the activation of purine nucleosides in tumor cells. The goal of these studies is to fully characterize the biochemical pharmacology of purine nucleoside analogs that can be used as prodrugs. These studies will support the overall goal of the NCDDG by supplying the biochemical information that is necessary for the rational development of this strategy for the treatment of cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA067763-07
Application #
6450654
Study Section
Project Start
2001-05-03
Project End
2002-04-30
Budget Start
Budget End
Support Year
7
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
Southern Research Institute
Department
Type
DUNS #
006900526
City
Birmingham
State
AL
Country
United States
Zip Code
35205

  Publications

Hassan, Abdalla E A; Abou-Elkhair, Reham A I; Parker, William B et al. (2016) 6-Methylpurine derived sugar modified nucleosides: Synthesis and evaluation of their substrate activity with purine nucleoside phosphorylases. Bioorg Chem 65:9-16
Hassan, Abdalla E A; Abou-Elkhair, Reham A I; Riordan, James M et al. (2012) Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides. Eur J Med Chem 47:167-74
Kang, You-Na; Zhang, Yang; Allan, Paula W et al. (2010) Structure of grouper iridovirus purine nucleoside phosphorylase. Acta Crystallogr D Biol Crystallogr 66:155-62
Tai, C-K; Wang, W; Lai, Y-H et al. (2010) Enhanced efficiency of prodrug activation therapy by tumor-selective replicating retrovirus vectors armed with the Escherichia coli purine nucleoside phosphorylase gene. Cancer Gene Ther 17:614-23
Hassan, Abdalla E A; Parker, William B; Allan, Paula W et al. (2009) Regioselective metalation of 6-methylpurines: synthesis of fluoromethyl purines and related nucleosides for suicide gene therapy of cancer. Nucleosides Nucleotides Nucleic Acids 28:642-56
Sorscher, E J; Harris, J; Alexander, M et al. (2006) Activators of viral gene expression in polarized epithelial monolayers identified by rapid-throughput drug screening. Gene Ther 13:781-8
Dontsova, Maria V; Gabdoulkhakov, Azat G; Molchan, Olga K et al. (2005) Preliminary investigation of the three-dimensional structure of Salmonella typhimurium uridine phosphorylase in the crystalline state. Acta Crystallogr Sect F Struct Biol Cryst Commun 61:337-40
Silamkoti, A V; Allan, P W; Hassan, A E A et al. (2005) Synthesis and biological activity of 2-fluoro adenine and 6-methyl purine nucleoside analogs as prodrugs for suicide gene therapy of cancer. Nucleosides Nucleotides Nucleic Acids 24:881-5
Toms, Angela V; Wang, Weiru; Li, Yingbo et al. (2005) Novel multisubstrate inhibitors of mammalian purine nucleoside phosphorylase. Acta Crystallogr D Biol Crystallogr 61:1449-58
Zang, Yang; Wang, Wen-Hu; Wu, Shaw-Wen et al. (2005) Identification of a subversive substrate of Trichomonas vaginalis purine nucleoside phosphorylase and the crystal structure of the enzyme-substrate complex. J Biol Chem 280:22318-25

Showing the most recent 10 out of 29 publications