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Related Concept Videos

Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
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Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
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Published on: April 15, 2013

Can nucleotides prevent Cu-induced oxidative damage?

Rozena Baruch-Suchodolsky1, Bilha Fischer

  • 1Department of Chemistry, Gonda-Goldschmied Medical Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.

Journal of Inorganic Biochemistry
|February 8, 2008
PubMed
Summary
This summary is machine-generated.

Natural and synthetic nucleotides and phosphates can inhibit copper-induced hydroxyl radical formation, preventing oxidative damage. Adenosine 5′-[beta,gamma-imino] triphosphate (AMP-PNP) showed the highest antioxidant activity, outperforming Trolox.

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Published on: August 1, 2015

Area of Science:

  • Biochemistry
  • Oxidative Stress Research
  • Medicinal Chemistry

Background:

  • Copper (Cu)-induced oxidative damage is linked to various diseases, including cancer, diabetes, and neurodegenerative disorders.
  • Existing copper chelators often lack biocompatibility or disrupt essential metal-ion homeostasis.
  • There is a critical need for effective and safe copper chelators with antioxidant properties.

Purpose of the Study:

  • To investigate the potential of natural and synthetic nucleotides and inorganic phosphates as inhibitors of copper-induced hydroxyl radical (•OH) formation.
  • To evaluate their efficacy in preventing oxidative damage via Fenton and Haber-Weiss mechanisms.
  • To identify novel, biocompatible copper chelators with antioxidant capabilities.

Main Methods:

  • Electron Spin Resonance (ESR) spectroscopy was employed to monitor copper-induced •OH production from hydrogen peroxide (H₂O₂) decomposition.
  • The inhibitory effects of various nucleotides and phosphates on Cu(I)/Cu(II)-catalyzed reactions were quantified using IC₅₀ values.
  • Structure-activity relationships were explored by comparing the inhibitory potential of different nucleotide analogs.

Main Results:

  • Adenosine triphosphate (ATP) and its analogs, including adenosine 5'-beta,gamma-methylene triphosphate (AMP-PCP), adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S), ADP, and tripolyphosphate, demonstrated significant inhibition of Cu-induced •OH formation.
  • Adenosine 5'-[beta,gamma-imino] triphosphate (AMP-PNP) emerged as the most potent inhibitor, with an IC₅₀ of 0.05 mM in the Cu(I)-H₂O₂ system, exhibiting 15-fold higher activity than Trolox.
  • Inhibition occurred via an ion chelation mechanism, requiring at least two phosphate groups for effective Fenton reaction inhibition.

Conclusions:

  • Nucleotides and phosphates effectively inhibit copper-induced hydroxyl radical formation at sub-millimolar concentrations.
  • These compounds represent promising candidates for preventing copper-mediated oxidative damage and related diseases.
  • The findings highlight the therapeutic potential of nucleotide-based compounds as biocompatible antioxidants.