Category: 55662-66-3

Fu, Dragony; Samson, Leona D. published an article in 2012, the title of the article was Direct repair of 3,N 4-ethenocytosine by the human ALKBH2 dioxygenase is blocked by the AAG/MPG glycosylase.Recommanded Product: 55662-66-3 And the article contains the following content:

Exocyclic ethenobases are highly mutagenic DNA lesions strongly implicated in inflammation and vinyl chloride-induced carcinogenesis. While the alkyladenine DNA glycosylase, AAG (or MPG), binds the etheno lesions 1,N 6-ethenoadenine (εA) and 3,N 4-ethenocytosine (εC) with high affinity, only εA can be excised to initiate base excision repair. Here, we discover that the human AlkB homolog 2 (ALKBH2) dioxygenase enzyme catalyzes direct reversal of εC lesions in both double- and single-stranded DNA with comparable efficiency to canonical ALKBH2 substrates. Notably, we find that in vitro, the non-enzymic binding of AAG to εC specifically blocks ALKBH2-catalyzed repair of εC but not that of methylated ALKBH2 substrates. These results identify human ALKBH2 as a repair enzyme for mutagenic εC lesions and highlight potential consequences for substrate-binding overlap between the base excision and direct reversal DNA repair pathways. 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 alkbh2 dioxygenase human dna repair ethenocytosine inhibition aag glycosylase, Enzymes: Separation-Purification-General Characterization and other aspects.Recommanded Product: 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On October 1, 2007, Srinath, Thiruneelakantan; Bharti, Sanjay Kumar; Varshney, Umesh published an article.Synthetic Route of 55662-66-3 The title of the article was Substrate specificities and functional characterization of a thermo-tolerant uracil DNA glycosylase (UdgB) from Mycobacterium tuberculosis. And the article contained the following:

Uracil DNA glycosylases (UDGs) excise uracil from DNA and initiate the base (uracil) excision repair pathway. Ung, a highly conserved protein, is the only UDG characterized so far in mycobacteria. Here, we show that Rv1259 from Mycobacterium tuberculosis codes for a double-stranded DNA (dsDNA) specific UDG (MtuUdgB). MtuUdgB is thermo-tolerant, contains Fe-S cluster and, in addition to uracil, it excises ethenocytosine and hypoxanthine from dsDNA. MtuUdgB is product inhibited by AP-site containing dsDNA but not by uracil. While MtuUdgB excises uracil present as a single-nucleotide bulge in dsDNA, it is insensitive to inhibition by dsDNA containing AP-site in the bulge. Interestingly, in the presence of cellular factors, the uracil excision activity of MtuUdgB is enhanced, and when introduced into E. coli (ung-), it rescues its mutator phenotype and prevents C to T mutations in DNA. Novel features of the mechanism of action of MtuUdgB and the physiol. significance of the family 5 UDG in mycobacteria have been discussed. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Synthetic Route of 55662-66-3

The Article related to thermotolerant uracil dna glycosylase udgb mycobacterium, Enzymes: Separation-Purification-General Characterization and other aspects.Synthetic Route of 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On November 30, 1996, Mueller, Michael; Hutchinson, Linda K.; Guengerich, F. Peter published an article.Category: imidazoles-derivatives The title of the article was Addition of Deoxyribose to Guanine and Modified DNA Bases by Lactobacillus helveticus trans-N-Deoxyribosylase. And the article contained the following:

The use of bacterial trans-N-deoxyribosylase was evaluated as an alternative method for deoxyribosylation in the synthesis of deoxyribonucleosides containing potentially mutagenic adducts. A crude enzyme preparation was isolated from Lactobacillus helveticus and compared to Escherichia coli purine nucleoside phosphorylase. Trans-N-deoxyribosylase was more regioselective than purine nucleoside phosphorylase in the deoxyribosylation of Gua at the N9 atom, as compared to N7, as demonstrated by NMR anal. of the product. 5,6,7,9-Tetrahydro-7-acetoxy-9-oxoimidazo[1,2-a]purine was efficiently deoxyribosylated by trans-N-deoxyribosylase but not at all by purine nucleoside phosphorylase. Other substrates for trans-N-deoxyribosylase were N2-(2-oxoethyl)Gua, pyrimido[1,2-a]purin-10(3H)-one, 1,N2-ε-Gua, N2,3-ε-Gua, 3,N4-ε-Cyt, 1,N6-ε-Ade, C8-methylGua, and C8-aminoGua, most of which gave the desired isomer (bond at the nitrogen corresponding to N9 in Gua) in good yield. Neither N7-alkylpurines nor C8-(arylamino)-substituted guanines were substrates. The approach offers a relatively convenient method of enzymic preparation of many carcinogen-DNA adducts at the nucleoside level, for either use as standards or incorporation into oligonucleotides. Trans-N-deoxyribosylase can also be used to remove deoxyribose from modified deoxyribonucleosides in the presence of excess Cyt. 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 deoxyribose dna base preparation trans deoxyribosylase, Enzymes: Separation-Purification-General Characterization and other aspects.Category: imidazoles-derivatives

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Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On October 18, 2002, Kavli, Bodil; Sundheim, Ottar; Akbari, Mansour; Otterlei, Marit; Nilsen, Hilde; Skorpen, Frank; Aas, Per Arne; Hagen, Lars; Krokan, Hans E.; Slupphaug, Geir published an article.Product Details of 55662-66-3 The title of the article was hUNG2 Is the Major Repair Enzyme for Removal of Uracil from U:A Matches, U:G Mismatches, and U in Single-stranded DNA, with hSMUG1 as a Broad Specificity Backup. And the article contained the following:

HUNG2 and hSMUG1 are the only known glycosylases that may remove uracil from both double- and single-stranded DNA in nuclear chromatin, but their relative contribution to base excision repair remains elusive. The present study demonstrates that both enzymes are strongly stimulated by physiol. concentrations of Mg2+, at which the activity of hUNG2 is 2-3 orders of magnitude higher than of hSMUG1. Moreover, Mg2+ increases the preference of hUNG2 toward uracil in ssDNA nearly 40-fold. APE1 has a strong stimulatory effect on hSMUG1 against dsU, apparently because of enhanced dissociation of hSMUG1 from AP sites in dsDNA. HSMUG1 also has a broader substrate specificity than hUNG2, including 5-hydroxymethyluracil and 3,N4-ethenocytosine. HUNG2 is excluded from, whereas hSMUG1 accumulates in, nucleoli in living cells. In contrast, only hUNG2 accumulates in replication foci in the S-phase. HUNG2 in nuclear extracts initiates base excision repair of plasmids containing either U:A and U:G in vitro. Moreover, an addnl. but delayed repair of the U:G plasmid is observed that is not inhibited by neutralizing antibodies against hUNG2 or hSMUG1. We propose a model in which hUNG2 is responsible for both prereplicative removal of deaminated cytosine and postreplicative removal of misincorporated uracil at the replication fork. We also provide evidence that hUNG2 is the major enzyme for removal of deaminated cytosine outside of replication foci, with hSMUG1 acting as a broad specificity backup. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Product Details of 55662-66-3

The Article related to uracil dna glycosylase ung2 base excision repair, Enzymes: Separation-Purification-General Characterization and other aspects.Product Details of 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On November 10, 1998, Hang, B.; Medina, M.; Fraenkel-Conrat, H.; Singer, B. published an article.Application of 55662-66-3 The title of the article was A 55-kDa protein isolated from human cells shows DNA glycosylase activity toward 3,N4-ethenocytosine and the G/T mismatch. And the article contained the following:

Etheno adducts in DNA arise from multiple endogenous and exogenous sources. Of these adducts we have reported that, 1,N6-ethenoadenine (εA) and 3,N4-ethenocytosine (εC) are removed from DNA by two sep. DNA glycosylases. We later confirmed these results by using a gene knockout mouse lacking alkylpurine-DNA-N-glycosylase, which excises εA. The present work is directed toward identifying and purifying the human glycosylase activity releasing εC. HeLa cells were subjected to multiple steps of column chromatog., including two εC-DNA affinity columns, which resulted in >1,000-fold purification Isolation and renaturation of the protein from SDS/polyacrylamide gel showed that the εC activity resides in a 55-kDa polypeptide. This apparent mol. mass is approx. the same as reported for the human G/T mismatch thymine-DNA glycosylase. This latter activity copurified to the final column step and was present in the isolated protein band having εC-DNA glycosylase activity. In addition, oligonucleotides containing εC·G or G/T(U), could compete for εC protein binding, further indicating that the εC-DNA glycosylase is specific for both types of substrates in recognition. The same substrate specificity for εC also was observed in a recombinant G/T mismatch DNA glycosylase from the thermophilic bacterium, Methanobacterium thermoautotrophicum THF. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Application of 55662-66-3

The Article related to ethenocytosine dna glycosylase purification, Enzymes: Separation-Purification-General Characterization and other aspects.Application of 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On April 15, 2011, Lingaraju, Gondichatnahalli M.; Davis, C. Ainsley; Setser, Jeremy W.; Samson, Leona D.; Drennan, Catherine L. published an article.Reference of Imidazo[1,2-c]pyrimidin-5(6H)-one The title of the article was Structural Basis for the Inhibition of Human Alkyladenine DNA Glycosylase (AAG) by 3,N4-Ethenocytosine-containing DNA. And the article contained the following:

Reactive oxygen and nitrogen species, generated by neutrophils and macrophages in chronically inflamed tissues, readily damage DNA, producing a variety of potentially genotoxic etheno base lesions; such inflammation-related DNA damage is now known to contribute to carcinogenesis. Although the human alkyladenine DNA glycosylase (AAG) can specifically bind DNA containing either 1,N6-ethenoadenine (εA) lesions or 3,N4-ethenocytosine (εC) lesions, it can only excise εA lesions. AAG binds very tightly to DNA containing εC lesions, forming an abortive protein-DNA complex; such binding not only shields εC from repair by other enzymes but also inhibits AAG from acting on other DNA lesions. To understand the structural basis for inhibition, we have characterized the binding of AAG to DNA containing εC lesions and have solved a crystal structure of AAG bound to a DNA duplex containing the εC lesion. This study provides the first structure of a DNA glycosylase in complex with an inhibitory base lesion that is induced endogenously and that is also induced upon exposure to environmental agents such as vinyl chloride. We identify the primary cause of inhibition as a failure to activate the nucleotide base as an efficient leaving group and demonstrate that the higher binding affinity of AAG for εC vs. εA is achieved through formation of an addnl. hydrogen bond between Asn-169 in the active site pocket and the O2 of εC. This structure provides the basis for the design of AAG inhibitors currently being sought as an adjuvant for cancer chemotherapy. 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 antitumor design ethenocytosine alkyladenine dna glycosylase inhibitor, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Reference of Imidazo[1,2-c]pyrimidin-5(6H)-one

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On May 1, 2003, Hardeland, Ulrike; Bentele, Marc; Jiricny, Josef; Schaer, Primo published an article.Name: Imidazo[1,2-c]pyrimidin-5(6H)-one The title of the article was The versatile thymine DNA-glycosylase: a comparative characterization of the human, Drosophila and fission yeast orthologs. And the article contained the following:

Human thymine-DNA glycosylase (TDG) is well known to excise thymine and uracil from G·T and G·U mismatches, resp., and was therefore proposed to play a central role in the cellular defense against genetic mutation through spontaneous deamination of 5-methylcytosine and cytosine. In this study, we characterized two newly discovered orthologs of TDG, the Drosophila melanogaster Thd1p and the Schizosaccharomyces pombe Thp1p proteins, with an objective to address the function of this subfamily of uracil-DNA glycosylases from an evolutionary perspective. A systematic biochem. comparison of both enzymes with human TDG revealed a number of biol. significant facts. (i) All eukaryotic TDG orthologs have broad and species-specific substrate spectra that include a variety of damaged pyrimidine and purine bases; (ii) the common most efficiently processed substrates of all are uracil and 3,N4-ethenocytosine opposite guanine and 5-fluorouracil in any double-stranded DNA context; (iii) 5-methylcytosine and thymine derivatives are processed with an appreciable efficiency only by the human and the Drosophila enzymes; (iv) none of the proteins is able to hydrolyze a non-damaged 5′-methylcytosine opposite G; and (v) the double strand and mismatch dependency of the enzymes varies with the substrate and is not a stringent feature of this subfamily of DNA glycosylases. These findings advance our current view on the role of TDG proteins and document that they have evolved with high structural flexibility to counter a broad range of DNA base damage in accordance with the specific needs of individual species. 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 uracil thymine dna glycosylase human drosophila fission yeast, schizosaccharomyces uracil dna glycosylase, Enzymes: Substrates-Cofactors-Inhibitors-Activators-Coenzymes-Products and other aspects.Name: Imidazo[1,2-c]pyrimidin-5(6H)-one

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Borys-Brzywczy, Ewa; Arczewska, Katarzyna D.; Saparbaev, Murat; Hardeland, Ulrike; Schaer, Primo; Kusmierek, Jaroslaw T. published an article in 2005, the title of the article was Mismatch dependent uracil/thymine-DNA glycosylases excise exocyclic hydroxyethano and hydroxypropano cytosine adducts.HPLC of Formula: 55662-66-3 And the article contains the following content:

Exocyclic adducts of DNA bases, such as etheno- and hydroxyalkano- ones, are generated by a variety of bifunctional agents, including endogenously formed products of lipid peroxidation In this work we selectively modified cytosines in the 5′-d(TTT TTT CTT TTT CTT TTT CTT TTT T)-3′ oligonucleotide using: chloroacetaldehyde to obtain 3,N4-α-hydroxyethano- (HEC) and 3,N4-etheno- (εC), acrolein to obtain. 3,N4-α-hydroxypropano- (HPC) and crotonaldehyde to obtain 3,N4-α-hydroxy-γ-methylpropano- (mHPC) adducts of cytosine. The studied adducts are alkali-labile which results in oligonucleotide strain breaks at the sites of modification upon strong base treatment. The oligonucleotides carrying adducted cytosines were studied as substrates of Escherichia coli Mug, human TDG and fission yeast Thp1p glycosylases. All the adducts studied are excised by bacterial Mug although with various efficiency: εC > HEC > HPC > mHPC. The yeast enzyme excises efficiently εC ≥ HEC > HPC, whereas the human enzyme excises only εC. The pH-dependence curves of excision of εC, HEC and HPC by Mug are bell shaped and the most efficient excision of adducts occurs within the pH range of 8.6-9.6. The observed increase of excision of HEC and HPC above pH 7.2 can be explained by deprotonation of these adducts, which are high pKa compounds and exist in a protonated form at neutrality. On the other hand, since εC is in a neutral form in the pH range studied, we postulate an involvement of an addnl. catalytic factor. We hypothesize that the enzyme structure undergoes a pH-induced rearrangement allowing the participation of Lys68 of Mug in catalysis via a hydrogen bond interaction of its ε-amino group with N4 of the cytosine exocyclic adducts. 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 mismatch uracil thymine dna glycosylase hydroxyethano hydroxypropano cytosine, Enzymes: Substrates-Cofactors-Inhibitors-Activators-Coenzymes-Products and other aspects.HPLC of Formula: 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On October 5, 2004, Guliaev, Anton B.; Singer, B.; Hang, Bo published an article.SDS of cas: 55662-66-3 The title of the article was Chloroethylnitrosourea-derived ethano cytosine and adenine adducts are substrates for Escherichia coli glycosylases excising analogous etheno adducts. And the article contained the following:

Exocyclic ethano DNA adducts are saturated etheno ring derivatives formed mainly by therapeutic chloroethylnitrosoureas (CNUs), which are also mutagenic and carcinogenic. In this work, we report that two of the ethano adducts, 3,N4-ethanocytosine (EC) and 1,N6-ethanoadenine (EA), are novel substrates for the Escherichia coli mismatch-specific uracil-DNA glycosylase (Mug) and 3-methyladenine DNA glycosylase II (AlkA), resp. It has been shown previously that Mug excises 3,N4-ethenocytosine (εC) and AlkA releases 1,N6-ethenoadenine (εA). Using synthetic oligonucleotides containing a single ethano or etheno adduct, we found that both glycosylases had a ∼20-fold lower excision activity toward EC or EA than that toward their structurally analogous εC or εA adduct. Both enzymes were capable of excising the ethano base paired with any of the four natural bases, but with varying efficiencies. The Mug activity toward EC could be stimulated by E. coli endonuclease IV and, more efficiently, by exonuclease III. Mol. dynamics (MD) simulations showed similar structural features of the etheno and ethano derivatives when present in DNA duplexes. However, also as shown by MD, the stacking interaction between the EC base and Phe 30 in the Mug active site is reduced as compared to the εC base, which could account for the lower EC activity observed in this study. 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 dna repair methyladenine uracil dna glycosylase ethanocytosine ethanoadenine, Enzymes: Substrates-Cofactors-Inhibitors-Activators-Coenzymes-Products and other aspects.SDS of cas: 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Maciejewska, Agnieszka M.; Poznanski, Jaroslaw; Kaczmarska, Zuzanna; Krowisz, Beata; Nieminuszczy, Jadwiga; Polkowska-Nowakowska, Agnieszka; Grzesiuk, Elzbieta; Kusmierek, Jaroslaw T. published an article in 2013, the title of the article was AlkB Dioxygenase Preferentially Repairs Protonated Substrates.Synthetic Route of 55662-66-3 And the article contains the following content:

Efficient repair by Escherichia coli AlkB dioxygenase of exocyclic DNA adducts 3,N4-ethenocytosine, 1,N6-ethenoadenine, 3,N4-α-hydroxyethanocytosine, and reported here for the first time 3,N4-α-hydroxypropanocytosine, requires higher Fe(II) concentration than the reference 3-methylcytosine. The pH optimum for the repair follows the order of pKa values for protonation of the adduct, suggesting that pos. charged substrates favorably interact with the neg. charged carboxylic group of Asp-135 side chain in the enzyme active center. This interaction is supported by mol. modeling, indicating that 1,N6-ethenoadenine and 3,N4-ethenocytosine are bound to AlkB more favorably in their protonated cationic forms. An anal. of the pattern of intermol. interactions that stabilize the location of the ligand points to a role of Asp-135 in recognition of the adduct in its protonated form. Moreover, ab initio calculations also underline the role of substrate protonation in lowering the free energy barrier of the transition state of epoxidation of the etheno adducts studied. The observed time courses of repair of mixtures of stereoisomers of 3,N4-α-hydroxyethanocytosine or 3,N4-α-hydroxypropanocytosine are unequivocally two-exponential curves, indicating that the resp. isomers are repaired by AlkB with different efficiencies. Mol. modeling of these adducts bound by AlkB allowed evaluation of the participation of their possible conformational states in the enzymic reaction. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Synthetic Route of 55662-66-3

The Article related to alkb dioxygenase recognition exocyclic dna adduct protonation, Enzymes: Substrates-Cofactors-Inhibitors-Activators-Coenzymes-Products and other aspects.Synthetic Route of 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem