Synthesis of 2-Azido-1,N<sup>6</sup>-Etheno and 2-Azido Analogs of Deoxyadenosine as Nucleotide Photoaffinity Probes

Flaherty, D.; Balse, Preeti; Li, Ké; Moore, Bob M.; Doughty, Michael B.

doi:10.1080/15257779508014653

Cited by 8 publications

(2 citation statements)

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“…[92] Imidazo [1,6]purines 93 readily underwent pyrimidine ring cleavage in alkaline media at room temperature, giving diimidazoles 94 [93,94] in 66-95 % yields. The ring opening products could be further transformed into imidazotriazines 95, [95,96] 2-thioimidazopurines 96 [97,98] or 2-deuteroimidazopurines 97 [99,100] (Scheme 16).…”

Section: Ring Opening Of Fused Purinesmentioning

confidence: 99%

Applications of Purine Ring Opening in the Synthesis of Imidazole, Pyrimidine, and New Purine Derivatives

et al. 2021

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Purines, which are regarded as relatively stable heterocyclic systems, can be opened at both pyrimidine and imidazole rings. Purine ring opening also serves as a tool for the preparation of ring-modified purines through rearrangement/recyclization mechanisms. The obtained imidazole, pyrimidine, and purine derivatives are privileged molecular scaffolds in medicinal and agricultural chemistry. Purine ring-opening approach is a useful alternative for their synthesis, which competes well with de novo approach or modification of a conserved heterocyclic core. The substitution patterns and groups that activate purines towards ring opening are reviewed. Moreover, mechanistic studies using labelled substrates, which are leading to rearranged purine derivatives are covered. Furthermore, an insight into imidazole ring opening upon exposure of purine system to DNA damaging agents is provided.

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Section: Ring Opening Of Fused Purinesmentioning

confidence: 99%

Applications of Purine Ring Opening in the Synthesis of Imidazole, Pyrimidine, and New Purine Derivatives

et al. 2021

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“…One approach to the identification of molecular contacts between polymerases and their substrates is nucleotide photoaffinity labeling. Examples of deoxynucleotide photoprobes available for this task include 8-and 2-azido-2′-deoxyadenosine phosphates (Evans & Coleman, 1989;Flaherty et al, 1995;Rush & Konigsberg, 1990) and more recently photoprobes based on TTP (Cheng et al, 1993;Satav et al, 1990) and its analogs, particularly 5-iodo- (Willis et al, 1993) and 5-azido-dUTP (Evans & Haley, 1987).…”

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confidence: 99%

Deoxyadenosine-Based DNA Polymerase Photoprobes: Design, Synthesis, and Characterization as Inhibitors of theEscherichia coliDNA Polymerase I Klenow Fragment^,

Moore¹,

Li²,

Doughty³

1996

Biochemistry

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DNA polymerase photoprobes 2-[(4-azidophenacyl)thio]-2'-deoxyadenosine 5'-triphosphate (1), 2-[(4-azidophenylsulfenyl)thio]-2'-deoxyadenosine 5'-triphosphate (2), and 2-[(4-azido-2-nitrophenyl)-thio]-2'-deoxyadenosine 5'-triphosphate (3) were designed from a thermodynamic model of DNA polymerase 1-substrate interactions such that the triphosphate would anchor the inhibitor and allow the phenyl azide to interact with the complementary template binding site. Photoprobes 1-3 were synthesized by condensation of 2-thio-2'-deoxyadenosine or its phosphate with p-azidophenacyl bromide, N-(4-azidophenylsulfenyl)phthalimide, and 4-azido-1-fluoro-2-nitrobenzene, respectively, and characterized as reversible and photoinduced irreversible inhibitors of the DNA polymerase I Klenow fragment and HIV I reverse transcriptase. The aryl azides decomposed with irradiation at 300 and 350 nm with half-lives ranging from 0.98 to 2.33 min and 2.15 to 5.38 min, respectively, with quantum efficiencies ranging from 0.29 to 0.55 and no apparent photodecomposition of the 2-thio-2'-deoxyadenosine nucleotide. Photoprobes 1-3 showed mixed noncompetitive inhibition of the Klenow fragment polymerase activity versus poly(dA).(T)10 as variable substrate with apparent competitive inhibition constants of 2.1, 36, and 29 microM, respectively, evidence suggesting that these photoprobes bind to both the free enzyme form and the enzyme-template-primer binary complex. Of the three photoprobes, only nucleotide 1 photoinactivates the Klenow fragment; in the presence of a 200-fold excess of nitrene scavenger, photoprobe 1 inactivates 92% of the Klenow fragment polymerase activity with saturation observed at 9.7 microM and an IC50 of about 2 microM. This evidence demonstrates that photoprobe 1 does bind to the Klenow fragment in the absence of template-primer and that it is an efficient photoprobe.

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N-Bromoacetamide

Virgil¹,

Corbu²,

Arseniyadis³

2008

Encyclopedia of Reagents for Organic Synthesis

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Synthesis of 2-Azido-1,N⁶-Etheno and 2-Azido Analogs of Deoxyadenosine as Nucleotide Photoaffinity Probes

Cited by 8 publications

References 19 publications

Applications of Purine Ring Opening in the Synthesis of Imidazole, Pyrimidine, and New Purine Derivatives

Applications of Purine Ring Opening in the Synthesis of Imidazole, Pyrimidine, and New Purine Derivatives

Deoxyadenosine-Based DNA Polymerase Photoprobes: Design, Synthesis, and Characterization as Inhibitors of theEscherichia coliDNA Polymerase I Klenow Fragment^,

N-Bromoacetamide

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Synthesis of 2-Azido-1,N6-Etheno and 2-Azido Analogs of Deoxyadenosine as Nucleotide Photoaffinity Probes

Cited by 8 publications

References 19 publications

Applications of Purine Ring Opening in the Synthesis of Imidazole, Pyrimidine, and New Purine Derivatives

Applications of Purine Ring Opening in the Synthesis of Imidazole, Pyrimidine, and New Purine Derivatives

Deoxyadenosine-Based DNA Polymerase Photoprobes: Design, Synthesis, and Characterization as Inhibitors of theEscherichia coliDNA Polymerase I Klenow Fragment,

N-Bromoacetamide

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Product

Resources

About

Synthesis of 2-Azido-1,N⁶-Etheno and 2-Azido Analogs of Deoxyadenosine as Nucleotide Photoaffinity Probes

Deoxyadenosine-Based DNA Polymerase Photoprobes: Design, Synthesis, and Characterization as Inhibitors of theEscherichia coliDNA Polymerase I Klenow Fragment^,