Syntheses and properties of adenine and thymine nucleoside alkyl phosphotriesters, the neutral analogs of dinucleoside monophosphates

Paul S. Miller, Kai N. Fang, Norman S. Kondo, Paul O P Ts'o

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The methyl and ethyl phosphotriester derivatives of TpT and dApdA were synthesized and were obtained as a pair of diastereoisomers in each case. As shown by pmr, CD, and uv hypochromicity measurements, the conformations of the triesters in solution are quite similar to those of the parent diesters, although there is less base stacking in the triesters. The phosphate-alkyl groups serve as monitors for the interaction between the backbone and the bases. The pmr resonances of these groups provide valuable information about the dynamics of the dimer conformations. Thermal perturbation or denaturation by DMSO causes a loss of the stacked conformation and an overall rotation of the base planes about the C-O-P bonds of the pentose-phosphate backbone. The triesters of dApdA form complexes with poly(uridylic acid) in 0.01 M Mg2+ with a stoichiometry of 2U:1A. The parent diester, dApdA, forms a complex with identical stoichiometry and the secondary structures of all three complexes appear to be the same. The thermal stabilities of the 2 poly(U)-triester complexes are greater than that of the 2 poly(U)-dApdA complex due to decreased repulsion between the negatively charged phosphates of the poly(U) and the neutral phosphotriester backbone. The phosphotriesters are stable in neutral aqueous solutions and are resistant to hydrolysis by snake venom and spleen phosphodiesterase, and by micrococcal nuclease.

Original languageEnglish (US)
Pages (from-to)6657-6665
Number of pages9
JournalJournal of the American Chemical Society
Issue number24
StatePublished - 1971


ASJC Scopus subject areas

  • Chemistry(all)

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