31077-24-4

Upstream product

• 124-09-4 1,6-Hexanediamine 
• 14985-44-5 8-bromo-2'-deoxyadenosine 
• 60-24-2 2-hydroxyethanethiol 
• 958-09-8 2'-deoxy-D-adenosine 
• 15731-72-3 2'-deoxyadenosine 3'-monophosphate 
• 653-63-4 2'-deoxyadenosine-5'-monophosphoric acid 
• 23339-45-9 2'-deoxyadenylyl(3'-5')-2'-deoxyadenosine 

Downstream Products

• 210825-01-7 N-(4-benzyloxy-3,5-dibromobenzyl)-8-oxoadenine 
• 210825-00-6 N-(4-benzyloxy-3,5-dibromobenzyl)-2'-deoxy-8-oxoadenosine 
• 1069110-42-4 5'-KP-8-oxodA 
• 778510-91-1 3'-O-tert-butyldimethylsilyl-7,8-dihydro-8-oxodeoxyadenosine 5'-[ethyl N-(N-trityl-L-prolyl)phosphoroamidate] 

Relevant academic research and scientific papers

Selective one-electron oxidation of duplex DNA oligomers: Reaction at thymines

The one-electron oxidation of duplex DNA generates a nucleobase radical cation (electron hole ) that migrates long distances by a hopping mechanism. The radical cation reacts irreversibly with H2O or O 2 to form oxidation products (damaged bases). In normal DNA (containing the four common DNA bases), reaction occurs most frequently at guanine. However, in DNA duplexes that do not contain guanine (i.e., those comprised exclusively of A/T base pairs), we discovered that reaction occurs primarily at thymine and gives products resulting from oxidation of the T-C5 methyl group and from addition to its C5-C6 double bond. This surprising result shows that it is the relative reactivity, not the stability, of a nucleobase radical cation that determines the nature of the products formed from oxidation of DNA. A mechanism for reaction is proposed whereby a thymine radical cation may either lose a proton from its methyl group or H2O/O2 may add across its double bond. In the latter case, addition may initiate a tandem reaction that converts both thymines of a TT step to oxidation products. The Royal Society of Chemistry.

Oxidative damage to DNA constituents by iron-mediated Fenton reactions: The deoxyadenosine family

The effect of exposing 2′-deoxyadenosine (dA), 5′-dAMP, 3′-dAMP, dApA, dA(pdA)19, and poly(dA): oligo(dT) to iron/H2O2 in the presence and absence of ethanol or NADH has been studied. HPLC retention times, enzyme treatments, radiolabeled substrates, UV absorption spectra, and fast atom bombardment mass spectrometry (FABMS) have been used to distinguish 20 products arising from the reaction, of which 16 have been identified and four anomers proposed by comparison with earlier gamma radiation studies. The radical responsible for the reactions seems to be analogous to radiation-derived ·OH, has many products in common, but has some novel ones probably specific for Fenton-induced damage. Two new dimeric adducts arising from the generation of hydroxylamine at N7 and its subsequent condensation with two known sugar damage products, dR-adenine-N1-oxide, and two isomers of dR-FAPy arising from radical attacks at C4 and C5, may be considered novel in the present study. Unlike radiation-derived ·OH, the radical under study is difficult to eliminate due to its generation in the proximity of the substrate molecules. It is proposed that the iron binds to the phosphate group and generates the radical in its vicinity. Strand breaks in dA(pdA)11 resulting from the Fenton reaction are of two types, spontaneous and alkali-labile. Duplex DNA is less sensitive to attack by this radical, as its various degradation products are a subset of those obtained with monomer substrates and only dR-FAPy production is relatively enhanced for poly (dA): oligo (dT) as compared to those from other substrates. Copyright

Radiation-induced formation of purine 5′,8-cyclonucleosides in isolated and cellular DNA: High stereospecificity and modulating effect of oxygen

The present work is aimed at gaining conclusive mechanistic insights into the radiation-induced formation of the 5′R and 5′S diastereomers of both adenine and guanine 5′,8-cyclo-2′-deoxyribonucleosides, with emphasis on the delineation of the inhibitory effect of O2 in isolated and cellular DNA. The levels of purine 5′,8-cyclo-2′- deoxyribonucleosides as assessed by HPLC-MS/MS were found to decrease steadily with the increase of O2 concentration, the 5′,8-cyclo-2′- deoxyguanosine being produced more efficiently than the 5′,8-cyclo- 2′-deoxyadenosine for low O2 concentrations. A high stereoselectivity was observed in the intramolecular addition of the C5′ radical to the C8 of the purine leading, after the creation of the C5′-C8 bond and a subsequent oxidation step, to the predominant formation of the 5′R diastereomer for both purine 5′,8-cyclonucleosides. The reduced formation yield of the 4 tandem lesions in the presence of O2 explains, at least partly, the low efficiency of radiation-induced yields of the purine 5′,8-cyclo-2′-deoxyribonucleosides in cellular DNA, which are about two orders of magnitude lower than the previously reported data obtained from HPLC-MS analysis. The Royal Society of Chemistry 2010.

A facile one-pot synthesis of 8-oxo-7,8-dihydro-(2′-deoxy)adenosine in water

Reaction of 2-mercaptoethanol with 8-bromo-2′-deoxyadenosine and 8-bromo-adenosine in aqueous solution and in the presence of triethylamine gave the 8-oxo-adenine derivatives in very good yields. Some mechanistic details are reported.

Convenient synthesis of 8-amino-2′-deoxyadenosine

We studied the behaviour of 8-azido-2′-deoxyadenosine and 8-bromo-2′-deoxyadenosine in aqueous solutions of ammonia and primary and secondary amines. Unexpectedly, 8-Azido-2′-deoxyadenosine is converted to 8-amino-2′-deoxyadenosine in excellent yields. The use of this reaction for the preparation of 8-aminoadenine derivatives needed for the preparation of oligonucleotides carrying 8-aminoadenine is discussed.

The equine estrogen metabolite 4-hydroxyequilenin causes DNA single- strand breaks and oxidation of DNA bases in vitro

Premarin (Wyeth-Ayerst) is the estrogen replacement treatment of choice and continues to be one of the most widely dispensed prescriptions in North America. In addition to endogenous estrogens, Premarin contains unsaturated equine estrogens, including equilenin [1,3,5(10),6,8-estrapentaen-3-ol-17- one]. In previous work, we showed that the equilenin metabolite 4- hydroxyequilenin (4-OHEN) can be autoxidized to 4-OHEN-o-quinone which readily entered into a redox couple with the semiquinone radical catalyzed by NAD(P)H, P450 reductase, or quinone reductase, resulting in generation of reactive oxygen species [Shen, L., Pisha, E., Huang, Z., Pezzuto, J. M., Krol, E., Alam, Z., van Breemen, R. B., and Bolton, J. L. (1997) Carcinogenesis 18, 1093-1101]. As oxidative damage to DNA by reactive oxygen species generated by redox active compounds has been proposed to lead to tumor formation, we investigated whether 4-OHEN could cause DNA damage. We treated λ phage DNA with 4-OHEN and found that extensive single-strand breaks could be obtained with increasing concentrations of 4-OHEN as well as increasing incubation times. If scavengers of reactive oxygen species are included in the incubations, DNA could be completely protected from 4-OHEN- mediated damage. In contrast, NADH and CuCl2 enhanced the ability of 4-OHEN to cause DNA single-strand breaks presumably due to redox cycling between 4- OHEN and the semiquinone radical generating hydrogen peroxide and ultimately copper peroxide complexes. We also confirmed that 4-OHEN could oxidize DNA bases since hydrolysis of 4-OHEN-treated calf thymus DNA and HPLC separation with electrospray MS detection revealed oxidized deoxynucleosides, including 8-oxodeoxyguanosine and 8-oxodeoxyadenosine. Our data suggest that DNA single-strand breaks and oxidation of DNA bases by 4-OHEN could contribute to the carcinogenic mechanism(s) of equine estrogens.