Category: 55662-66-3

On December 31, 2000, Petronzelli, Fiorella; Riccio, Antonio; Markham, George D.; Seeholzer, Steven H.; Genuardi, Maurizio; Karbowski, Mariola; Yeung, Anthony T.; Matsumoto, Yoshihiro; Bellacosa, Alfonso published an article.Reference of Imidazo[1,2-c]pyrimidin-5(6H)-one The title of the article was Investigation of the substrate spectrum of the human mismatch-specific DNA N-glycosylase MED1 (MBD4): fundamental role of the catalytic domain. And the article contained the following:

The human DNA repair protein MED1 (also known as MBD4) was isolated as an interactor of the mismatch repair protein MLH1 in a yeast two-hybrid screening. MED1 has a tripartite structure with an N-terminal 5-methylcytosine binding domain (MBD), a central region, and a C-terminal catalytic domain with homol. to bacterial DNA damage-specific glycosylases/lyases. Indeed, MED1 acts as a mismatch-specific DNA N-glycosylase active on thymine, uracil, and 5-fluorouracil paired with guanine. The glycosylase activity of MED1 preferentially targets G:T mismatches in the context of CpG sites; this indicates that MED1 is involved in the repair of deaminated 5-methylcytosine. Interestingly, frameshift mutations of the MED1 gene have been reported in human colorectal, endometrial, and pancreatic cancers. For its putative role in maintaining genomic fidelity at CpG sites, it is important to characterize the biochem. properties and the substrate spectrum of MED1. Here we show that MED1 works under a wide range of temperature and pH, and has a limited optimum range of ionic strength. MED1 has a weak glycosylase activity on the mutagenic adduct 3,N4-ethenocytosine, a metabolite of vinyl chloride and Et carbamate. The differences in glycosylase activity on G:U and G:T substrates are not related to differences in substrate binding and likely result from intrinsic differences in the chem. step. Finally, the isolated catalytic domain of MED1 retains the preference for G:T and G:U substrates in the context of methylated or unmethylated CpG sites. This suggests that the catalytic domain is fundamental, and the 5-methylcytosine binding domain dispensable, in determining the substrate spectrum of MED1. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Reference of Imidazo[1,2-c]pyrimidin-5(6H)-one

The Article related to dna glycosylase med1 catalytic domain substrate specificity, mbd4 dna glycosylase catalytic domain substrate specificity, Enzymes: Structure-Conformation-Active Site and other aspects.Reference of Imidazo[1,2-c]pyrimidin-5(6H)-one

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On December 1, 1999, Barrett, Tracey E.; Scharer, Orlando D.; Savva, Renos; Brown, Tom; Jiricny, Josef; Verdine, Gregory L.; Pearl, Laurence H. published an article.Name: Imidazo[1,2-c]pyrimidin-5(6H)-one The title of the article was Crystal structure of a thwarted mismatch glycosylase DNA repair complex. And the article contained the following:

The bacterial mismatch-specific uracil-DNA glycosylase (MUG) and eukaryotic thymine-DNA glycosylase (TDG) enzymes form a homologous family of DNA glycosylases that initiate base-excision repair of G:U/T mismatches. Despite low sequence homol., the MUG/TDG enzymes are structurally related to the uracil-DNA glycosylase enzymes, but have a very different mechanism for substrate recognition. We have now determined the crystal structure of the Escherichia coli MUG enzyme complexed with an oligonucleotide containing a non-hydrolysable deoxyuridine analog mismatched with guanine, providing the first structure of an intact substrate-nucleotide productively bound to a hydrolytic DNA glycosylase. The structure of this complex explains the preference for G:U over G:T mispairs, and reveals an essentially non-specific pyrimidine-binding pocket that allows MUG/TDG enzymes to excise the alkylated base, 3,N4-ethenocytosine. Together with structures for the free enzyme and for an abasic-DNA product complex, the MUG-substrate analog complex reveals the conformational changes accompanying the catalytic cycle of substrate binding, base excision and product release. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Name: Imidazo[1,2-c]pyrimidin-5(6H)-one

The Article related to crystal structure uracil dna glycosylase complex, dna uracil glycosylase conformation repair mechanism, Enzymes: Structure-Conformation-Active Site and other aspects.Name: Imidazo[1,2-c]pyrimidin-5(6H)-one

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On October 22, 1999, Lutsenko, Eugene; Bhagwat, Ashok S. published an article.Quality Control of Imidazo[1,2-c]pyrimidin-5(6H)-one The title of the article was The role of the Escherichia coli Mug protein in the removal of uracil and 3,N4-ethenocytosine from DNA. And the article contained the following:

The human thymine-DNA glycosylase has a sequence homolog in Escherichia coli that is described to excise uracils from U路G mismatches (Gallinari, P., and Jiricny, J. (1996) Nature 383, 735-738) and is named mismatched uracil glycosylase (Mug). It has also been described to remove 3,N4-ethenocytosine (蔚C) from 蔚C路G mismatches (Saparbaev, M., and Laval, J. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 8508-8513). We used a mug mutant to clarify the role of this protein in DNA repair and mutation avoidance. We find that inactivation of mug has no effect on C to T or 5-methylcytosine to T mutations in E. coli and that this contrasts with the effect of ung defect on C to T mutations and of vsr defect on 5-methylcytosine to T mutations. Even under conditions where it is overproduced in cells, Mug has little effect on the frequency of C to T mutations. Because uracil-DNA glycosylase (Ung) and Vsr are known to repair U路G and T路G mismatches, resp., we conclude that Mug does not repair U路G or T路G mismatches in vivo. A defect in mug also has little effect on forward mutations, suggesting that Mug does not play a role in avoiding mutations due to endogenous damage to DNA in growing E. coli. Cell-free extracts from mug+ ung cells show very little ability to remove uracil from DNA, but can excise 蔚C. The latter activity is missing in extracts from mug cells, suggesting that Mug may be the only enzyme in E. coli that can remove this mutagenic adduct. Thus, the principal role of Mug in E. coli may be to help repair damage to DNA caused by exogenous chem. agents such as chloroacetaldehyde. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Quality Control of Imidazo[1,2-c]pyrimidin-5(6H)-one

The Article related to escherichia dna repair mismatched uracil glycosylase mug protein ethenocytosine, General Biochemistry: Subcellular Processes and other aspects.Quality Control of Imidazo[1,2-c]pyrimidin-5(6H)-one

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Latifi, Reza; Minnick, Jennifer L.; Quesne, Matthew G.; de Visser, Sam P.; Tahsini, Laleh published an article in 2020, the title of the article was Computational studies of DNA base repair mechanisms by nonheme iron dioxygenases: selective epoxidation and hydroxylation pathways.HPLC of Formula: 55662-66-3 And the article contains the following content:

DNA base repair mechanisms of alkylated DNA bases is an important reaction in chem. biol. and particularly in the human body. It is typically catalyzed by an ä¼?ketoglutarate-dependent nonheme iron dioxygenase named the AlkB repair enzyme. In this work we report a detailed computational study into the structure and reactivity of AlkB repair enzymes with alkylated DNA bases. In particular, we investigate the aliphatic hydroxylation and C=C epoxidation mechanisms of alkylated DNA bases by a high-valent iron(IV)-oxo intermediate. Our computational studies use quantum mechanics/mol. mechanics methods on full enzymic structures as well as cluster models on active site systems. The work shows that the iron(IV)-oxo species is rapidly formed after dioxygen binding to an iron(IV) center and passes a bicyclic ring structure as intermediate. Subsequent cluster models explore the mechanism of substrate hydroxylation and epoxidation of alkylated DNA bases. The work shows low energy barriers for substrate activation and consequently energetically feasible pathways are predicted. Overall, the work shows that a high-valent iron(IV)-oxo species can efficiently dealkylate alkylated DNA bases and return them into their original form. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).HPLC of Formula: 55662-66-3

The Article related to human dioxygenase alkb dna base repair mechanism epoxidation hydroxylation, Enzymes: Structure-Conformation-Active Site and other aspects.HPLC of Formula: 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On August 19, 2013, Li, Deyu; Fedeles, Bogdan I.; Shrivastav, Nidhi; Delaney, James C.; Yang, Xuedong; Wong, Cintyu; Drennan, Catherine L.; Essigmann, John M. published an article.Safety of Imidazo[1,2-c]pyrimidin-5(6H)-one The title of the article was Removal of N-Alkyl Modifications from N2-Alkylguanine and N4-Alkylcytosine in DNA by the Adaptive Response Protein AlkB. And the article contained the following:

The AlkB enzyme is an Fe(II)- and ä¼?ketoglutarate-dependent dioxygenase that repairs DNA alkyl lesions by a direct reversal of damage mechanism as part of the adaptive response in E. coli. The reported substrate scope of AlkB includes simple DNA alkyl adducts, such as 1-methyladenine, 3-methylcytosine, 3-ethylcytosine, 1-methylguanine, 3-methylthymine, and N6-methyladenine, as well as more complex DNA adducts, such as 1,N6-ethenoadenine, 3,N4-ethenocytosine, and 1,N6-ethanoadenine. Previous studies have revealed, in a piecemeal way, that AlkB has an impressive repertoire of substrates. The present study makes two additions to this list, showing that alkyl adducts on the N2 position of guanine and N4 position of cytosine are also substrates for AlkB. Using high resolution ESI-TOF mass spectrometry, we show that AlkB has the biochem. capability to repair in vitro N2-methylguanine, N2-ethylguanine, N2-furan-2-yl-methylguanine, N2-tetrahydrofuran-2-yl-methylguanine, and N4-methylcytosine in ssDNA but not in dsDNA. When viewed together with previous work, the exptl. data herein demonstrate that AlkB is able to repair all simple N-alkyl adducts occurring at the Watson-Crick base pairing interface of the four DNA bases, confirming AlkB as a versatile gatekeeper of genomic integrity under alkylation stress. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Safety of Imidazo[1,2-c]pyrimidin-5(6H)-one

The Article related to alkyl alkylguanine alkylcytosine dna adaptation protein alkb dioxygenase, Enzymes: Analysis (Determination-Detection) and other aspects.Safety of Imidazo[1,2-c]pyrimidin-5(6H)-one

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On August 1, 2012, Tudek, Barbara; Speina, Elzbieta published an article.Formula: C6H5N3O The title of the article was Oxidatively damaged DNA and its repair in colon carcinogenesis. And the article contained the following:

A review. Inflammation, high fat, high red meat and low fiber consumption have for long been known as the most important etiol. factors of sporadic colorectal cancers (CRC). Colon cancer originates from neoplastic transformation in a single layer of epithelial cells occupying colonic crypts, in which migration and apoptosis program becomes disrupted. This results in the formation of polyps and metastatic cancers. Mutational program in sporadic cancers involves APC gene, in which mutations occur most abundantly in the early phase of the process. This is followed by mutations in RAS, TP53, and other genes. Progression of carcinogenic process in the colon is accompanied by augmentation of the oxidative stress, which manifests in the increased level of oxidatively damaged DNA both in the colon epithelium, and in blood leukocytes and urine, already at the earliest stages of disease development. Defense mechanisms are deregulated in CRC patients: (i) antioxidative vitamins level in blood plasma declines with the development of disease; (ii) mRNA level of base excision repair enzymes in blood leukocytes of CRC patients is significantly increased; however, excision rate is regulated sep., being increased for 8-oxoGua, while decreased for lipid peroxidation derived ethenoadducts, 蔚Ade and 蔚Cyt; (iii) excision rate of 蔚Ade and 蔚Cyt in colon tumors is significantly increased in comparison to asymptomatic colon margin, and ethenoadducts level is decreased. This review highlights mechanisms underlying such deregulation, which is the driving force to colon carcinogenesis. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Formula: C6H5N3O

The Article related to review colon rectum cancer oxidative stress dna repair, Mammalian Pathological Biochemistry: Reviews and other aspects.Formula: C6H5N3O

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Tudek, Barbara; Winczura, Alicja; Janik, Justyna; Siomek, Agnieszka; Foksinski, Marek; Olinski, Ryszard published an article in 2010, the title of the article was Involvement of oxidatively damaged DNA and repair in cancer development and aging.Category: imidazoles-derivatives And the article contains the following content:

A review. DNA damage and DNA repair may mediate several cellular processes, like replication and transcription, mutagenesis and apoptosis and thus may be important factors in the development and pathol. of an organism, including cancer. DNA is constantly damaged by reactive oxygen species (ROS) and reactive nitrogen species (RNS) directly and also by products of lipid peroxidation (LPO), which form exocyclic adducts to DNA bases. A wide variety of oxidatively-generated DNA lesions are present in living cells. 8-Oxoguanine (8-oxoGua) is one of the best known DNA lesions due to its mutagenic properties. Among LPO-derived DNA base modifications the most intensively studied are ethenoadenine and ethenocytosine, highly miscoding DNA lesions considered as markers of oxidative stress and promutagenic DNA damage. Although at present it is impossible to directly answer the question concerning involvement of oxidatively damaged DNA in cancer etiol., it is likely that oxidatively modified DNA bases may serve as a source of mutations that initiate carcinogenesis and are involved in aging (i.e. they may be causal factors responsible for these processes). To counteract the deleterious effect of oxidatively damaged DNA, all organisms have developed several DNA repair mechanisms. The efficiency of oxidatively damaged DNA repair was frequently found to be decreased in cancer patients. The present work reviews the basis for the biol. significance of DNA damage, particularly effects of 8-oxoGua and ethenoadduct occurrence in DNA in the aspect of cancer development, drawing attention to the multiplicity of proteins with repair activities. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Category: imidazoles-derivatives

The Article related to review oxidative stress dna damage repair cancer aging, Mammalian Pathological Biochemistry: Reviews and other aspects.Category: imidazoles-derivatives

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On July 3, 2012, Mangericha, Aswin; Knutson, Charles G.; Parry, Nicola M.; Muthupalani, Sureshkumar; Ye, Wenjie; Prestwich, Erin; Cui, Liang; McFaline, Jose L.; Mobley, Melissa; Ge, Zhongming; Taghizadeh, Koli; Wishnok, John S.; Wogan, Gerald N.; Fox, James G.; Tannenbaum, Steven R.; Dedon, Peter C. published an article.SDS of cas: 55662-66-3 The title of the article was Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer. And the article contained the following:

Helicobacter hepaticus-infected Rag2-/- mice emulate many aspects of human inflammatory bowel disease, including the development of colitis and colon cancer. To elucidate mechanisms of inflammation-induced carcinogenesis, we undertook a comprehensive anal. of histopathol., mol. damage, and gene expression changes during disease progression in these mice. Infected mice developed severe colitis and hepatitis by 10 wk post-infection, progressing into colon carcinoma by 20 wk post-infection, with pronounced pathol. in the cecum and proximal colon marked by infiltration of neutrophils and macrophages. Transcriptional profiling revealed decreased expression of DNA repair and oxidative stress response genes in colon, but not in liver. Mass spectrometric anal. revealed higher levels of DNA and RNA damage products in liver compared to colon and infection-induced increases in 5-chlorocytosine in DNA and RNA and hypoxanthine in DNA. Paradoxically, infection was associated with decreased levels of DNA etheno adducts. Levels of nucleic acid damage from the same chem. class were strongly correlated in both liver and colon. The results support a model of inflammation-mediated carcinogenesis involving infiltration of phagocytes and generation of reactive species that cause local mol. damage leading to cell dysfunction, mutation, and cell death. There are strong correlations among histopathol., phagocyte infiltration, and damage chem. that suggest a major role for neutrophils in inflammation-associated cancer progression. Further, paradoxical changes in nucleic acid damage were observed in tissue- and chem.-specific patterns. The results also reveal features of cell stress response that point to microbial pathophysiol. and mechanisms of cell senescence as important mechanistic links to cancer. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).SDS of cas: 55662-66-3

The Article related to gene expression helicobacter infection stress dna damage colon carcinoma, Mammalian Pathological Biochemistry: Oncology and other aspects.SDS of cas: 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On September 15, 2010, Obtulowicz, Tomasz; Winczura, Alicja; Speina, Elzbieta; Swoboda, Maja; Janik, Justyna; Janowska, Beata; Ciesla, Jaroslaw M.; Kowalczyk, Pawel; Jawien, Arkadiusz; Gackowski, Daniel; Banaszkiewicz, Zbigniew; Krasnodebski, Ireneusz; Chaber, Andrzej; Olinski, Ryszard; Nair, Jagadesaan; Bartsch, Helmut; Douki, Thierry; Cadet, Jean; Tudek, Barbara published an article.Category: imidazoles-derivatives The title of the article was Aberrant repair of etheno-DNA adducts in leukocytes and colon tissue of colon cancer patients. And the article contained the following:

To assess the role of lipid peroxidation-induced DNA damage and repair in colon carcinogenesis, the excision rates and levels of 1,N6-etheno-2′-deoxyadenosine (蔚dA), 3,N4-etheno-2′-deoxycytidine (蔚dC), and 1,N2-etheno-2′-deoxyguanosine (1,N2-蔚dG) were analyzed in polymorphic blood leukocytes (PBL) and resected colon tissues of 54 colorectal carcinoma (CRC) patients and PBL of 56 healthy individuals. In PBL the excision rates of 1,N6-ethenoadenine (蔚Ade) and 3,N4-ethenocytosine (蔚Cyt), measured by the nicking of oligodeoxynucleotide duplexes with single lesions, and unexpectedly also the levels of 蔚dA and 1,N2-蔚dG, measured by LC/MS/MS, were lower in CRC patients than in controls. In contrast the mRNA levels of repair enzymes, alkylpurine- and thymine-DNA glycosylases and a basic site endonuclease (APE1), were higher in PBL of CRC patients than in those of controls, as measured by QPCR. In the target colon tissues 蔚Ade and 蔚Cyt excision rates were higher, whereas the 蔚dA and 蔚dC levels in DNA, measured by 32P-postlabeling, were lower in tumor than in adjacent colon tissue, although a higher mRNA level was observed only for APE1. This suggests that during the onset of carcinogenesis, etheno adduct repair in the colon seems to be under a complex transcriptional and posttranscriptional control, whereby deregulation may act as a driving force for malignancy. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Category: imidazoles-derivatives

The Article related to colon cancer base excision repair etheno dna adduct leukocyte, Mammalian Pathological Biochemistry: Oncology and other aspects.Category: imidazoles-derivatives

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On November 30, 2003, Barbin, Alain; Ohgaki, Hiroko; Nakamura, Jun; Kurrer, Michael; Kleihues, Paul; Swenberg, James A. published an article.Recommanded Product: 55662-66-3 The title of the article was Endogenous deoxyribonucleic acid (DNA) damage in human tissues: A comparison of ethenobases with aldehydic DNA lesions. And the article contained the following:

Two types of endogenous DNA lesions, ethenobases [1,N6-ethenoadenine (蔚A), 3,N4-ethenocytosine (蔚C)] and aldehydic DNA lesions (ADLs), were measured in several tissues (liver, lung, kidney, colon, colon mucosa, cerebellum, and gray and white matter of the cerebrum) obtained postmortem during autopsy examinations of 12 individuals (6 males, 6 females; ages, 58-87 yr). Issues relating to changes in levels of DNA damage with disease and after death were addressed. The extent of DNA damage in autopsy samples was not associated with the length of the postmortem interval and was similar to levels observed in surgery samples, suggesting that endogenous, steady-state levels of etheno adducts and of ADLs are relatively stable during the hours immediately after death. In this limited series of samples, and with a few possible exceptions, the disease status before death was not associated with increased endogenous DNA damage in the affected tissue. DNA ethenobases were lowest in the cerebellum (median molar ratios: 蔚A/A = 1.0 x 10-8; 蔚C/C = 1.9 x 10-8) and highest in the gray matter (蔚A/A = 2.9 x 10-8; 蔚C/C = 4.8 x 10-8) and white matter (蔚A/A = 2.4 x 10-8; 蔚C/C = 5.2 x 10-8) of the cerebrum. In other tissues, median values were 1.2-1.9 x 10-8 for 蔚A/A and 2.0-3.3 x 10-8 for 蔚C/C. There was a good correlation between the levels of 蔚A and 蔚C (r = 0.80, P < 0.0001). Levels of ADLs were similar in the liver, lung, kidney, and white matter of the cerebrum (median values: 5.7-7.9 ADLs/106 nucleotides), higher in the colon (11.3 x 10-6) and gray matter of the cerebrum (9.0 x 10-6) and lower in the cerebellum (3.7 x 10-6). There was no correlation between levels of ethenobases and amounts of ADLs (蔚A vs. ADLs: r = 0.12, P = 0.33; 蔚C vs. ADLs: r = 0.024, P = 0.85). Although there was an interindividual variability in the extent of endogenous DNA damage (4-fold for 蔚A and 蔚C, 2-fold for ADLs), which may be determined, in part, by the capacity to repair DNA and may be related to the pathol. or treatment of the patients, these results suggest that the cerebrum contains higher endogenous DNA damage than the other tissues. These data are in line with previous studies showing that brain tissues are more susceptible to oxidative stress and lipid peroxidation than other tissues. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Recommanded Product: 55662-66-3

The Article related to dna damage aldehydic lesion ethenobase disease cancer, Mammalian Pathological Biochemistry: Oncology and other aspects.Recommanded Product: 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem