BIOMAT Database Logo BIOMAT Database Logo

Inhibitory Effect of 8-Halogenated 7-Deaza-2'-deoxyguanosine Triphosphates on Human 8-Oxo-2'-deoxyguanosine Triphosphatase, hMTH1, Activities. 2016

Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

hMTH1 (8-oxo-2'-deoxyguanine triphosphatase) hydrolyzes oxidized nucleoside triphosphates; its presence is non-essential for survival of normal cells but is required for survival of cancer cells. In this study, 8-halogenated-7-deaza-2'-deoxyguanosine triphosphate (8-halogenated-7-deazadGTP) derivatives were synthesized. Interestingly, these triphosphates were poor substrates for hMTH1, but exhibited strong competitive inhibition against hMTH1 at nanomolar levels. This inhibitory effect is attributed to slower rate of hydrolysis, possibly arising from enzyme structural changes, specifically different stacking interactions with 8-halogenated-7-deazadGTP. This is the first example of using nucleotide derivatives to inhibit hMTH1, thus demonstrating their potential as antitumor agents.

UI MeSH Term Description Entries
D010744 Phosphoric Monoester Hydrolases A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. Phosphatase,Phosphatases,Phosphohydrolase,Phosphohydrolases,Phosphomonoesterase,Phosphomonoesterases,Phosphoric Monoester Hydrolase,Hydrolase, Phosphoric Monoester,Hydrolases, Phosphoric Monoester,Monoester Hydrolase, Phosphoric
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003848 Deoxyguanine Nucleotides Guanine nucleotides which contain deoxyribose as the sugar moiety. Deoxyguanosine Phosphates,Nucleotides, Deoxyguanine,Phosphates, Deoxyguanosine
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006219 Halogens A family of nonmetallic, generally electronegative, elements that form group 17 (formerly group VIIa) of the periodic table. Halogen,Group 17 Elements,Elements, Group 17
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D045643 DNA Repair Enzymes Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions. DNA Repair Enzyme,Enzyme, DNA Repair,Enzymes, DNA Repair,Repair Enzyme, DNA,Repair Enzymes, DNA

Related Publications

Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
7-Deaza-2'-deoxyguanosine.
March 2005, Acta crystallographica. Section C, Crystal structure communications,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
Oligonucleotide incorporation and base pair stability of 9-deaza-2'-deoxyguanosine, an analogue of 8-oxo-2'-deoxyguanosine.
August 2010, The Journal of organic chemistry,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors.
April 2001, Neuro-oncology,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
Human telomerase inhibition by 7-deaza-2'-deoxypurine nucleoside triphosphates.
December 1996, Biochemistry,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
Oligodeoxynucleotides containing C-7 propyne analogs of 7-deaza-2'-deoxyguanosine and 7-deaza-2'-deoxyadenosine.
August 1996, Nucleic acids research,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
Inhibition of human telomerase by 7-deaza-2'-deoxyguanosine nucleoside triphosphate analogs: potent inhibition by 6-thio-7-deaza-2'-deoxyguanosine 5'-triphosphate.
February 2001, Bioorganic chemistry,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
Alternating d(G-C)3 and d(C-G)3 hexanucleotides containing 7-deaza-2'-deoxyguanosine or 8-aza-7-deaza-2'-deoxyguanosine in place of dG.
February 1989, Nucleic acids research,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
7-Iodo-8-aza-7-deaza-2'-deoxyadenosine and 7-bromo-8-aza-7-deaza-2'-deoxyadenosine.
April 2000, Acta crystallographica. Section C, Crystal structure communications,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
[Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)].
November 2004, Nihon rinsho. Japanese journal of clinical medicine,
Yizhen Yin, and Shigeki Sasaki, and Yosuke Taniguchi
The alpha-D anomer of 5-aza-7-deaza-2'-deoxyguanosine.
March 2002, Acta crystallographica. Section C, Crystal structure communications,
Copied contents to your clipboard!