Chemistry

Inhibition of Metal-Mediated Oxidative DNA Damage: Probing a Potential Metal Coordination Mechanism through Isothermal Titration Calorimetry and Raman Spectroscopy

Document Type

Oral Presentation

Location

Indianapolis, IN

Subject Area

Chemistry

Start Date

13-4-2018 11:00 AM

End Date

13-4-2018 11:45 AM

Description

Metal-mediated oxidative DNA damage is due to metal ions, such as Fe (II), Cu (I), and Cu (II), reacting with H2O2 to form hydroxyl radicals (·OH) through the Fenton (or Fenton-like) reaction. This can be harmful to reproduction and translation of DNA causing both single and double stranded breakage as well as modifications to specific bases. This DNA damage is associated with cancer, Alzheimer’s disease, Rheumatoid arthritis, and congestive heart failure. It has been found with supplementary antioxidants that oxidative DNA damage can be minimized or inhibited. However, the mechanisms of complexation and associated binding constants are largely unknown. Isothermal titration calorimetry (ITC) is a method through which binding information (including stoichiometry and binding constants) can be obtained. ITC exhibits several distinct advantages when determining binding interactions in comparison to nuclear magnetic resonance spectroscopy, NMR. A sample for NMR analysis requires a much higher concentration in comparison to ITC, which is important with respect to this research because of the concentration ratio of free metal ion and the antioxidant in question. With a much higher sensitivity, the ITC ensures that with a significantly smaller sample volume, the instrument will generate accurate and reproducible results. This study focuses primarily on the interactions between the metal ions Fe(II), Cu(I), and Cu(II) with the sulfur-based antioxidants glutathione (GSH) and glutathione disulfide (GSSG). GSH and GSSG have been shown to exhibit antioxidant activity through a mechanism that involves metal ion coordination. Previous work in our laboratory using isothermal titration calorimetry, ITC, has established a binding interaction between Cu(II) and the sulfur compounds GSH and GSSG. Through Raman spectroscopy and ITC, we have found significant data measuring the interaction of free ions of copper (II) and their complexation with glutathione and glutathione disulfide.

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Apr 13th, 11:00 AM Apr 13th, 11:45 AM

Inhibition of Metal-Mediated Oxidative DNA Damage: Probing a Potential Metal Coordination Mechanism through Isothermal Titration Calorimetry and Raman Spectroscopy

Indianapolis, IN

Metal-mediated oxidative DNA damage is due to metal ions, such as Fe (II), Cu (I), and Cu (II), reacting with H2O2 to form hydroxyl radicals (·OH) through the Fenton (or Fenton-like) reaction. This can be harmful to reproduction and translation of DNA causing both single and double stranded breakage as well as modifications to specific bases. This DNA damage is associated with cancer, Alzheimer’s disease, Rheumatoid arthritis, and congestive heart failure. It has been found with supplementary antioxidants that oxidative DNA damage can be minimized or inhibited. However, the mechanisms of complexation and associated binding constants are largely unknown. Isothermal titration calorimetry (ITC) is a method through which binding information (including stoichiometry and binding constants) can be obtained. ITC exhibits several distinct advantages when determining binding interactions in comparison to nuclear magnetic resonance spectroscopy, NMR. A sample for NMR analysis requires a much higher concentration in comparison to ITC, which is important with respect to this research because of the concentration ratio of free metal ion and the antioxidant in question. With a much higher sensitivity, the ITC ensures that with a significantly smaller sample volume, the instrument will generate accurate and reproducible results. This study focuses primarily on the interactions between the metal ions Fe(II), Cu(I), and Cu(II) with the sulfur-based antioxidants glutathione (GSH) and glutathione disulfide (GSSG). GSH and GSSG have been shown to exhibit antioxidant activity through a mechanism that involves metal ion coordination. Previous work in our laboratory using isothermal titration calorimetry, ITC, has established a binding interaction between Cu(II) and the sulfur compounds GSH and GSSG. Through Raman spectroscopy and ITC, we have found significant data measuring the interaction of free ions of copper (II) and their complexation with glutathione and glutathione disulfide.