Proton nuclear magnetic resonance study of the self-complementary hexanucleotide d(pTpA)3 and its interaction with daunomycin Academic Article uri icon

abstract

  • The helix-coil transition of the self-complementary hexanucleotide d(pTpA)3 has been studied in 1 M NaCl by high-resolution proton nuclear magnetic resonance spectroscopy. Almost all of the 12 resonances deriving from the three environments of the four nucleotide protons have been assigned to the central, internal, or terminal nucleotides. At 5 degrees C, the effect of extensive fraying is evident since the central base pairs exhibit of extensive fraying is evident since the central base pairs exhibit only 20% of the chemical shifts observed for poly(dA-dT) . poly(dA-dT) accompanying denaturation. Daunomycin interacts with the hexanucleotide duplex at 5 degrees C and stabilizes it by 21 degrees C at a drug/nucleotide ratio of 0.063 (i.e., drug/hexanucleotide duplex ratio of 0.75). The chemical shifts of the drug protons suggest that ring D of daunomycin does not overlap significantly with the central base pairs of the hexanucleotide and that it extends out from the "helix". This information, together with studies of space-filling models of the complex, suggests that rings B and C of daunomycin overlap with adjacent base pairs and are skewed with respect to the base pairs.

publication date

  • October 14, 1980