The structure of d(TpA), the major photoproduct of thymidylyl-(3'5')-deoxyadenosine

Nucleic Acids Res. 1996 Apr 15;24(8):1554-60. doi: 10.1093/nar/24.8.1554.

Abstract

Irradiation of the dinucleotide TpdA and TA-containing oligonucleotides and DNA produces the TA* photoproduct which was proposed to be the [2+2] cyclo-addition adduct between the C5-C6 double bonds of the T and the A [Bose,S.N., Kumar,S., Davies,R.J.H., Sethi,S.K. and McCloskey,J.A. (1984) Nucleic Acids Res. 12, 7929-7947]. The proposed structure was based on a variety of spectroscopic and chemical degradation studies, and the assignment of a trans-syn-I stereochemistry was based on an extensive 1H-NMR and molecular modeling study of the dinucleotide adduct [Koning,T.M.G., Davies,R.J.H. and Kaptein,R. (1990) Nucleic Acids Res. 18, 277-284]. However, a number of properties of TA* are not in accord with the originally proposed structure, and prompted a re-evaluation of the structure. To assign the 13C spectrum and establish the bond connectivities of the TA* photoproduct of TpdA [d(TpA)*], 1H-13C heteronuclear multiple-quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC) spectra were obtained. The 13C shifts and connectivities were found to be inconsistent with the originally proposed cyclobutane ring fusion between the thymine and adenine, but could be explained by a subsequent ring-expansion reaction to give an eight-membered ring valence isomer. The new structure for the d(TpA)* resolves the inconsistencies with the originally proposed structure, and could have a stereochemistry that arises from the anti, anti glycosyl conformation found in B form DNA.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbon Radioisotopes
  • Dinucleoside Phosphates / chemistry*
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Hydrogen
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides / chemistry*
  • Photochemistry

Substances

  • Carbon Radioisotopes
  • Dinucleoside Phosphates
  • Heterocyclic Compounds, 4 or More Rings
  • Oligodeoxyribonucleotides
  • d(TpA) thymine-adenine photoadduct
  • 2'-deoxythymidylyl-(3'-5')-2'-deoxyadenosine
  • deoxythymidylyl-3'-5'-deoxyadenylate
  • Hydrogen