In vitro nonenzymatic glycation of DNA nucleobases: an evaluation of advanced glycation end products under alkaline pH

Dutta, Udayan; Cohenford, Menashi A.; Guha, Madhumita; Dain, Joel A.
December 2006
Analytical & Bioanalytical Chemistry;Dec2006, Vol. 386 Issue 6, p1633
Academic Journal
The advanced glycation end products (AGEs) of DNA nucleobases have received little attention, perhaps due to the fact that adenine, guanine, cytosine and thymine do not dissolve under mild pH conditions. To maintain nucleobases in solution, alkaline pH conditions are typically required. The objectives of this investigation were twofold: to study the susceptibility of DNA nucleobases to nonenzymatic attack by different sugars, and to evaluate the factors that influence the formation of nucleobase AGEs at pH 12, i.e., in an alkaline environment that promotes the aldo–keto isomerization and epimerization of sugars. Varying concentrations of adenine, guanine, thymine and cytosine were incubated over time with constant concentrations of D-glucose, D-galactose or D/ L-glyceraldehyde under different conditions of temperature and ionic strength. Incubation of the nucleobases with the sugars resulted in a heterogeneous assembly of AGEs whose formation was monitored by UV/fluorescence spectroscopy. Capillary electrophoresis and HPLC were used to resolve the AGEs of the DNA adducts and provided a powerful tool for following the extent of glycation in each of the DNA nucleobases. Mass spectrometry studies of DNA adducts of guanine established that glycation at pH 12 proceeded through an Amadori intermediate.


Related Articles

  • Thymine-rich single-stranded DNA activates Mcm4/6/7 helicase on Y-fork and bubble-like substrates. Zhiying You; Yukio Ishimi; Takeshi Mizuno; Kaoru Sugasawa; Fumio Hanaoka; Hisao Masai // EMBO Journal;11/17/2003, Vol. 22 Issue 22, p6148 

    The presence of multiple clusters of runs of asymmetric adenine or thymine is a feature commonly found in eukaryotic replication origins. Here we report that the helicase and ATPase activities of the mammalian Mcm4/6/7 complex are activated specifically by thymine stretches. The Mcm helicase is...

  • Polaron Hopping in Nano-scale Poly(dA)–Poly(dT) DNA. Singh, Mahi R.; Bart, Graeme; Zinke-Allmang, Martin // Nanoscale Research Letters;Mar2010, Vol. 5 Issue 3, p501 

    We investigate the current–voltage relationship and the temperature-dependent conductance of nano-scale samples of poly(dA)–poly(dT) DNA molecules. A polaron hopping model has been used to calculate the I–V characteristic of nano-scale samples of DNA. This model agrees with...

  • Opinion: Why are there four letters in the genetic alphabet? Szathm´ry, Eörs // Nature Reviews Genetics;Dec2003, Vol. 4 Issue 12, p995 

    We list, without thinking, the four base types that make up DNA as adenine, guanine, cytosine and thymine. But why are there four? This question is now all the more relevant as organic chemists have synthesized new base pairs that can be incorporated into nucleic acids. Here, I argue that there...

  • base pair (bp):. Schlegel, Rolf H. J. // Encyclopedic Dictionary of Plant Breeding & Related Subjects;2003, p52 

    A definition of the term "base pair" is presented. It refers to the nitrogenous bases of adenine-thymine/uracil; guaninecytosine that pair in double-stranded DNA or RNA molecules; 1,000 bp = 1 kb. The term is used in the field of genetics.

  • tetranucleotide theory (early 1900s) Biology.  // Dictionary of Theories;2002, p521 

    A definition of the term "tetranucleotide theory" is presented. It refers to a biology-based theory which states about the presence of adenine, cytosine, guanine, and thymine in deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), in equimolar amounts. The theory was replaced by Chargaff's...

  • Analysis of the Main Nucleosides in Cordyceps Sinensis by LC/ESI-MS. Jian-Wei Xie; Lan-Fang Huang; Wei Hu; Yun-Biao He; Kin Ping Wong // Molecules;Jan2010, Vol. 15 Issue 1, p305 

    A sensitive, selective and reliable liquid chromatography-mass spectrometry coupled with electrospray ionization interface method for simultaneous separation and determination of thymine, adenine, adenosine and cordycepin in Cordyceps sinensis has been established. The optimum separation for...

  • A new twist to an old tale: The influence of the exchange of thymine for adenine on the stability... Mills, Marin; Klump, Horst H. // South African Journal of Chemistry;Dec97, Vol. 50 Issue 4, p184 

    Examines the influence of exchanging thymines for adenine on the stability of a purine motif DNA triple helix. Melting behavior of reference purine triplex and intramolecular pyrimidine triplex; Increase of thermal stability due to favorable stacking interactions gained by introducing the large...

  • Localized melting of duplex DNA by Cdc6/Orc1 at the DNA replication origin in the hyperthermophilic archaeon Pyrococcus furiosus. Matsunaga, Fujihiko; Takemura, Kie; Akita, Masaki; Adachi, Akinori; Yamagami, Takeshi; Ishino, Yoshizumi // Extremophiles;Jan2010, Vol. 14 Issue 1, p21 

    The initiation step is a key process to regulate the frequency of DNA replication. Although recent studies in Archaea defined the origin of DNA replication ( oriC) and the Cdc6/Orc1 homolog as an origin recognition protein, the location and mechanism of duplex opening have remained unclear. We...

  • Computational and Empirical Trans-hydrogen Bond Deuterium Isotope Shifts Suggest that N1�N3 A:U Hydrogen Bonds of RNA are Shorter than those of A:T Hydrogen Bonds of DNA. Yong-Ick Kim; Manalo, Marlon; Per�z, Lisa; LiWang, Andy // Journal of Biomolecular NMR;Apr2006, Vol. 34 Issue 4, p229 

    Density functional theory calculations of isolated Watson�Crick A:U and A:T base pairs predict that adenine 13C2 trans-hydrogen bond deuterium isotope shifts due to isotopic substitution at the pyrimidine H3, 2h?13C2, are sensitive to the hydrogen-bond distance between the N1 of adenine and...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics