Effect of glycation on the structure and dynamics of DNA: a critical spectroscopic approach

J Phys Chem B. 2007 Jan 25;111(3):646-51. doi: 10.1021/jp063206g.

Abstract

Glycated DNA is considered to be a pathogenic factor for diabetes mellitus. Here we present a novel and preliminary study on normal and glycated (with fructose and glucose-6-phosphate as reducing sugars) human placenta DNA using agarose gel electrophoresis and photon correlation spectroscopy. The former is used to find structural alterations, while the latter is exploited to observe differences in the dynamics between normal (i.e., pure) and glycated DNA molecules. For scattering angles up to 90 degrees , we obtained a quasi-single-exponential relaxation process for the pure DNA, whereas at higher scattering angles the relaxation of pure DNA becomes broader with a stretching parameter beta approximately 0.6 at 130 degrees. Interestingly, for both the glycated DNAs stretched relaxation profiles and higher relaxation rates (Omega) are observed for all scattering angles. Moreover, a separate and very fast relaxation (e.g., relaxation time tau approximately 2 micros at 90 degrees ) can be noticed for both the glycated DNAs at all the studied scattering angles. Thus, the dramatic changes in the relaxation parameters (Omega, tau, and beta) of the glycated DNA show at the molecular level, for the first time, that the structure and dynamics of DNA are strongly affected by glycation. Implications of the results are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Algorithms
  • DNA / chemistry*
  • Electrophoresis, Agar Gel
  • Energy Transfer
  • Ethidium
  • Female
  • Fluorescent Dyes
  • Fructose / chemistry
  • Glucose / chemistry
  • Glucose-6-Phosphate / chemistry
  • Humans
  • Nucleic Acid Conformation
  • Placenta / chemistry
  • Pregnancy
  • Spectrometry, Fluorescence
  • Ultraviolet Rays

Substances

  • Fluorescent Dyes
  • Fructose
  • Glucose-6-Phosphate
  • DNA
  • Ethidium
  • Glucose