14985-44-5

Usage

Uses

8-Bromo-2’deoxyadenosine is a brominated DNA adducts generated by human DNA polymerases.

Upstream product

• 958-09-8 2'-deoxy-D-adenosine 

Downstream Products

• 149540-21-6 5-(6-amino-8-bromo-9H-purin-9-yl)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)tetrahydrofuran-3-ol 
• 117182-88-4 (5'S)-5',8-cyclo-2'-deoxyadenosine 
• 958-09-8 2'-deoxy-D-adenosine 
• 127133-10-2 8-Amino-2',3'-dideoxyadenosine 
• 131265-35-5 8-Azido-2'-deoxyadenosine 
• 1062513-32-9 8-N-(4-methoxyphenyl)-3',5'-O-bis(tert-butyldimethylsilyl)-2'-deoxyadenosine 
• 1062513-34-1 8-N-4-aminobiphenyl-3’,5’-O-bis(tert-butyldimethylsilyl)-2’-deoxyadenosine 
• 1367204-19-0 N⁶-dibenzoyl-8-N-(4-aminobiphenyl)-3’,5’-O-bis(tert-butyldimethylsilyl)-2’-deoxyadenosine 
• 1384847-31-7 N⁶-dibenzoyl-8-N-(2-aminofluorene)-3’,5’-O-bis(tert-butyldimethylsilyl)-2’-deoxyadenosine 
• 1367204-22-5 C₃₇H₅₂N₆O₅Si₂ 
• 1367204-25-8 C₃₉H₅₆N₆O₅Si₂ 
• 1367204-28-1 C₃₈H₅₄N₆O₆Si₂ 
• 1367204-31-6 C₄₃H₅₆N₆O₅Si₂ 
• 1384847-30-6 C₄₄H₅₆N₆O₅Si₂ 

Relevant academic research and scientific papers

Structure-activity relationships of bisphosphate nucleotide derivatives as P2Y1 receptor antagonists and partial agonists

The P2Y1 receptor is present in the heart, in skeletal and various smooth muscles, and in platelets, where its activation is linked to aggregation. Adenosine 3',5'- and 2',5'-bisphosphates have been identified as selective antagonists at the P2Y1 receptor (Boyer et al. Mol. Pharmacol. 1996, 50, 1323-1329) and have been modified structurally to increase receptor affinity (Camaioni et al. J. Med. Chem. 1998, 41, 183-190). We have extended the structure-activity relationships to a new series of deoxyadenosine bisphosphates with substitutions in the adenine base, ribose moiety, and phosphate groups. The activity of each analogue at P2Y1 receptors was determined by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit phospholipase C stimulation elicited by 10 nM 2-(methylthio)adenosine 5'-diphosphate (antagonist effect). 2'-Deoxyadenosine bisphosphate analogues containing halo, amino, and thioether groups at the 2-position of the adenine ring were more potent P2Y1 receptor antagonists than analogues containing various heteroatom substitutions at the 8-position. An N6-methyl-2-chloro analogue, 6, was a full antagonist and displayed an IC50 of 206 nM. Similarly, N6- methyl-2-alkylthio derivatives 10, 14, and 15 were nearly full antagonists of IC50 50 of 3 μM, i.e., similar in potency to ATP. 5'-Phosphate groups have been modified in the form of triphosphate, methyl phosphate, and cyclic 3',5'-diphosphate derivatives. The carbocyclic analogue had enhanced agonist efficacy, and the 5'-O-phosphonylmethyl modification was tolerated, suggesting that deviations from the nucleotide structure may result in improved utility as pharmacological probes. The N6-methoxy modification eliminated receptor affinity. Pyrimidine nucleoside 3',5'- bisphosphate derivatives were inactive as agonists or antagonists at P2Y receptor subtypes.

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.

Deoxyribonucleoside-modified squaraines as near-IR viscosity sensors

Deoxyribonucleoside-modified squaraines were synthesized by Sonogashira coupling reactions using an unsymmetrical, terminal alkynylated benzothiazolium squaraine dye. These non-natural nucleosides exhibited fluorescent 'turn-on' properties in viscous conditions with an enhancement of >300-fold. The viscosity-dependent fluorescence enhancement was attributed to a combination of hampering both molecular aggregation and intramolecular bond rotation of the squaraine probe. Fluorescence microscopy allowed visualization of highly viscous regions during various stages of cellular mitosis.

6-Nitrochrysene-Derived C8-2′-Deoxyadenosine Adduct: Synthesis of Site-Specific Oligodeoxynucleotides and Mutagenicity in Escherichia coli

6-Nitrochrysene (6-NC), the most potent carcinogen evaluated by the newborn mouse assay, is metabolically activated by nitroreduction and a combination of ring oxidation and nitroreduction pathways. The nitroreduction pathway yields three major DNA adducts: at the C8 and N2 positions of 2′-deoxyguanosine (dG), N-(dG-8-yl)-6-AC and 5-(dG-N2-yl)-6-AC, and at the C8 position of 2′-deoxyadenosine (dA), N-(dA-8-yl)-6-AC. A nucleotide excision repair assay demonstrated that N-(dA-8-yl)-6-AC is repaired much more slowly than many other bulky DNA adducts, including the other DNA adducts formed by 6-NC. But neither the total synthesis nor evaluation of other biological activities of this dA adduct has ever been reported. Herein, we report a convenient synthesis of the 6-NC-derived dA adduct by employing the Buchwald-Hartwig coupling strategy, which provided a high yield of the protected N-(dA-8-yl)-6-AC. The deprotected nucleoside showed syn conformational preference by NMR spectroscopy. Following DMT protection of the 5′-hydroxyl, N-(dA-8-yl)-6-AC was converted to its 3′-phosphoramidite, which was used to prepare oligonucleotides containing a single N-(dA-8-yl)-6-AC adduct. Circular dichroism spectra of the adducted duplex showed only a slight departure from the B-DNA helix profile of the control duplex. The 15-mer N-(dA-8-yl)-6-AC oligonucleotide was used to construct a single-stranded plasmid vector containing a single adduct, which was replicated in Escherichia coli. Viability of the adducted construct was ～60% of the control, indicating slower translesion synthesis of the adduct, which increased to nearly 90% upon induction of the SOS functions. Without SOS, the mutation frequency (MF) of the adduct was 5.2%, including 2.9% targeted and 2.3% semi-targeted mutations. With SOS, the targeted MF increased 3-fold to 9.0%, whereas semi-targeted mutation increased only marginally to 3.2%. The major type of targeted mutation was A*→G in both uninduced and SOS-induced cells.

Genotoxic C8-Arylamino-2′-deoxyadenosines Act as Latent Alkylating Agents to Induce DNA Interstrand Cross-Links

DNA interstrand cross-links (ICLs) are extremely deleterious and structurally diverse, driving the evolution of ICL repair pathways. Discovering ICL-inducing agents is, thus, crucial for the characterization of ICL repair pathways and Fanconi anemia, a ge

Influence of Linker Length on Ligase-Catalyzed Oligonucleotide Polymerization

Ligase-catalyzed oligonucleotide polymerization (LOOPER) that enables the sequence-defined generation of DNA with up to 16 different modifications has recently been developed. This approach was used to develop new classes of diversely modified DNA aptamer

Selective C8-Metalation of Purine Nucleosides via Oxidative Addition

8-Bromo-2′-deoxy-3′,5′-di-O-acetylguanosine (1), 8-bromo-2′,3′,5′-tri-O-acetylguanosine (2), 8-bromo-2′-deoxy-3′,5′-di-O-acetyladenosine (3), and 8-bromo-2′,3′,5′-tri-O-acetyladenosine (4) react with [Pd(PPh3)4] via a C8-Br oxidative addition to give the C8-palladated azolato complexes [5]-[8] featuring an unprotonated N7 ring nitrogen atom. The complexes feature diastereotopic trans-disposed triphenylphosphine ligands, which allowed the determination of 2JPP for complexes of the type trans-[PdL2(PPh3)2] (2JPP = 442 Hz for [7]). In addition, two complex molecules of [7] form a trans-Watson-Crick/Hoogsteen AA base pair in the solid state. N7-protonation of the guanosine-derived complexes [5] and [6] with HBF4·Et2O and of adenosine-derived complexes [7] and [8] using lutidinium triflate yields complexes [9]BF4 and [10]BF4 and complexes [11]OTf and [12]OTf bearing protic NH,NR-NHC ligands derived from guanosine and adenosine, respectively.

Diverse size approach to incorporate and extend highly fluorescent unnatural nucleotides into DNA

We have prepared a series of size-diverse unnatural nucleotides containing fluorescent (dApyrTP, dUpyrTP, dUantTP, dUthiTP) and quencher (dUazoTP) units, as well as nucleotides presenting small functional groups (dAethTP, dAoctTP, dUethTP, dUiodTP), all based on deoxyadenosine and deoxyuridine, and examined their suitability for use in enzymatic incorporation and extension into DNA. We observed a size-dependence of the incorporation and extension capability (following the order dUiodTP?=?dUethTP?=?dUthiTP?>?dUazoTP?>?dUpyrTP?>?dUantTP) during primer extension. This result was supported by circular dichroism (CD) spectra, which revealed a trend in the different B-form DNA structures depending on the size of the unit at the 5-position of the deoxyuridine (dUiodTP?>?dUethTP?>?dUthiTP?>?dUpyrTP), obtained from the PCR products. Interestingly, dUthiTP could be incorporated and extended into long DNA strands during primer extension and even PCR amplification, with CD spectroscopy confirming a stable secondary B-form duplex DNA structure. We observed full-length extension products even when combining dUthiTP with a template containing 24 continuous dA units during the primer extension. Thus, we believe that dUthiTP is a promising fluorescent nucleotide for a diverse range of biological applications requiring multiple incorporation and extension directly without disruption of B-form DNA structures.

G-Tetraplex-Induced FRET within Telomeric Repeat Sequences Using PyA-PerA as Energy Donor-Acceptor Pair

G-tetraplex induced fluorescence resonance energy transfer (FRET) within telomeric repeat sequences has been studied using a nucleoside-tethered FRET pair embedded in the human telomeric G-quadruplex forming sequence (5′-A GGG TTPyA GGG TTPerA GGG TTA GGG-3′, Py=pyrene, Per=perylene). Conformational change from a single strand to an anti-parallel G-quadruplex leads to FRET from energy donor (PyA) to acceptor (PerA). The distance between the FRET donor/acceptor partners was controlled by changing the number of G-quartet spacer units. The FRET efficiency decreases with increase in G-quartet units. Overall findings indicate that this could be further used for the development of FRET-based sensing and measurement techniques.

An efficient and facile methodology for bromination of pyrimidine and purine nucleosides with sodium monobromoisocyanurate (SMBI)

An efficient and facile strategy has been developed for bromination of nucleosides using sodium monobromoisocyanurate (SMBI). Our methodology demonstrates bromination at the C-5 position of pyrimidine nucleosides and the C-8 position of purine nucleosides. Unprotected and also several protected nucleosides were brominated in moderate to high yields following this procedure.