23662-75-1

Usage

Uses

Used in Cancer Research:
8-Methylguanine is utilized as a biomarker for DNA damage and mutations, serving as an indicator of exposure to mutagenic agents and a potential risk factor for cancer development. Its presence in DNA can be analyzed to study the mechanisms of carcinogenesis and the effectiveness of cancer prevention strategies.
Used in DNA Repair Mechanism Studies:
As a component involved in base excision repair, 8-methylguanine is used in research to understand the process of DNA repair. Studying its role can provide insights into the maintenance of genetic stability and the development of therapeutic approaches to modulate DNA repair pathways.
Used in Cancer Therapy:
8-Methylguanine is explored as a target in cancer therapy, specifically for its potential in inhibiting DNA repair processes. This application aims to increase the effectiveness of cancer treatments by preventing the repair of therapy-induced DNA damage, thereby enhancing the susceptibility of cancer cells to treatment.
Used in Pharmaceutical Development:
In the pharmaceutical industry, 8-methylguanine is used as a lead compound in the development of drugs that modulate DNA repair mechanisms. These drugs may have applications in synergizing with existing cancer therapies to improve patient outcomes by overcoming resistance and increasing the effectiveness of treatment.

InChI:InChI=1/C6H7N5O/c1-2-8-3-4(9-2)10-6(7)11-5(3)12/h1H3,(H4,7,8,9,10,11,12)

Upstream product

• 75-91-2 tert.-butylhydroperoxide 
• 961-07-9 2'-Deoxyguanosine 
• 113193-94-5 7-(methylthio)pterin 
• 113230-79-8 7-ethoxypterin 
• 113193-93-4 7-isopropoxypterin 
• 3149-34-6 7-methoxypterin 
• 85819-69-8 8-methyl-2'-deoxyguanosine 

Downstream Products

• 160948-27-6 O⁶-benzyl-8-methylguanine 

Relevant academic research and scientific papers

Stability of N-glycosidic bond of (5′ S)-8,5′-Cyclo-2′- deoxyguanosine

8,5′-Cyclopurine deoxynucleosides are unique tandem lesions containing an additional covalent bond between the base and the sugar. These mutagenic and genotoxic lesions are repaired only by nucleotide excision repair. The N-glycosidic (or C1′-N9) bond of 2′-deoxyguanosine (dG) derivatives is usually susceptible to acid hydrolysis, but even after cleavage of this bond of the cyclopurine lesions, the base would remain attached to the sugar. Here, the stability of the N-glycosidic bond and the products formed by formic acid hydrolysis of (5′S)-8,5′-cyclo-2′-deoxyguanosine (S-cdG) were investigated. For comparison, the stability of the N-glycosidic bond of 8,5′-cyclo-2′,5′-dideoxyguanosine (ddcdG), 8-methyl-2′-deoxyguanosine (8-Me-dG), 7,8-dihydro-8-oxo-2′- deoxyguanosine (8-Oxo-dG), and dG was also studied. In various acid conditions, S-cdG and ddcdG exhibited similar stability to hydrolysis. Likewise, 8-Me-dG and dG showed comparable stability, but the half-lives of the cyclic dG lesions were at least 5-fold higher than those of dG or 8-Me-dG. NMR studies were carried out to investigate the products formed after the cleavage of the C1′-N9 bond. 2-Deoxyribose generated α and β anomers of deoxyribopyranose and deoxyribopyranose oligomers following acid treatment. S-cdG gave α- and β-deoxyribopyranose linked guanine as the major products, but α and β anomers of deoxyribofuranose linked guanine and other products were also detected. The N-glycosidic bond of 8-Oxo-dG was found exceptionally stable in acid. Computational studies determined that both the protonation of the N7 atom and the rate constant in the bond breaking step control the overall kinetics of hydrolysis, but both varied for the molecules studied indicating a delicate balance between the two steps. Nevertheless, the computational approach successfully predicted the trend observed experimentally. For 8-Oxo-dG, the low pKa of O8 and N3 prevented appreciable protonation, making the free energy for N-glycosidic bond cleavage in the subsequent step very high.

Synthesis, miscoding specificity, and thermodynamic stability of oligodeoxynucleotide containing 8-methyl-2'-deoxyguanosine

8-Methyl-2'-deoxyguanosine (8-MedG) was synthesized by reacting dG under the methyl radical generating system and incorporated into oligodeoxynucleotides using phosphoramidite techniques. The site-specifically modified oligodeoxynucleotide containing a single 8-MedG was then used as a template for primer extension reactions catalyzed by the 3'-5' exonuclease- free (exo-) Klenow fragment of Escherichia coli DNA polymerase I and mammalian DNA polymerase α. Primer extension catalyzed by the exo- Klenow fragment readily passed the 8-MedG lesion in the template while that catalyzed by pol α was retarded opposite the lesion. The fully extended products formed during DNA synthesis were analyzed to quantify the miscoding specificities of 8-MedG. Both DNA polymerases incorporated primarily dCMP, the correct base opposite the lesion, along with small amounts of incorporation of dGMP and dAMP. In addition, two-base deletion was observed only when the exo- Klenow fragment was used. The thermodynamic stability of 8-MedG in the duplex was also studied. The duplex containing 8-MedG:dG was more thermally and thermodynamically stable than that of dG:dG. The duplex containing 8-MedG:dA was more thermodynamically stable than that of dG:dA. We conclude that 8-MedG is a miscoding lesion and capable of generating G → C and G → T transversions and deletion in cells.

RING TRANSFORMATION OF PTERINS TO GUANINES

7-Alkoxypterins undergo a ring contraction into guanine derivatives and demethoxylation by activated aluminum.