Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Post-synthetic Generation of Fapy-dG Lesion within Oligodeoxynucleotides: Differential Anomeric Impacts on DNA Duplex Properties

Cellular DNA is a target for oxidative stress arising from exposure to environmental and endogenous sources that account for thousands of oxidatively damaged bases per day. The prominent oxidative lesion, imidazole ring opened N6-(2-Deoxy-a,b-D-erythro-pentafuranosyl)-2,6-diamino-4-hydroxy-5-formylamidopyrimidine (Fapy-dG) is one of the most common lesions of this type (1). Its formation has been reported under various experimental conditions, and its accumulation is associated with progression of many age-related diseases and cancer (2, 3). Structural and thermodynamic studies of this lesion require development of universal and reliable synthetic strategy to incorporate cognate Fapy-dG site-specifically within any oligodeoxynucleotide sequence. We elaborated the scheme that consists of a two-step post-synthetic treatment of the modified nitropyrimidine oligonucleotide and does not require purification of the intermediate product (4). This approach has been successfully applied to the preparation of isotopically labeled Fapy-dG in DNA for subsequent solution state NMR studies. We demonstrated that the lesion exists in DNA in a several slowly interconverting anomeric and rotameric forms (4). The anomeric forms of the Fapy-dG containing synthetic oligonucleotides have been successfully separated using ion-exchange HPLC. The resultant anomeric duplexes exhibit distinct thermal and thermodynamic profiles that are characteristic of α- and β-anomers.


  1. M. Dizdaroglu, G.Kirkali, and P. Jaruga. Free Radical Biol. Med. 45, 1610–1621 (2008)
  2. J.Q. Wang, W.R. Markesbery, and M.A. Lovell, J. Neurochem. 96, 825–832 (2006).
  3. D.C. Malins, N,L. Polissar, and S.J. Gunselman, Proc. Natl Acad. Sci. USA 93, 2557–2563 (1996).
  4. M. Lukin, C.A.S.A. Minetti, D. P. Remeta, S. Attaluri, F. Johnson, K.J. Breslauer, and C. de los Santos. Nucl. Acids Res. 2011 (in press)

Mark Lukin*1
Conceição A. S. A. Minetti2
David P. Remeta2
Sivaprasad Attaluri1
Francis Johnson
1Kenneth J. Breslauer
2Carlos de los Santos1

1Department of Pharmacological Sciences
School of Medicine
Stony Brook University
Stony Brook, New York, 11794-8651 USA
2Department of Chemistry and Chemical Biology
Rutgers – The State University of New Jersey
Piscataway, New Jersey 08854, USA

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