Oligothymidylates Comportant La Structure Alternee Alkylphosphotriester-Phosphodiester Et Lies De Facon Covalente A Un Agent Intercalant

Abstract

Abstract Four oligothymidylates involving alternating alkylphosphotriester-phosphodiester backbones with the same steric configuration for all the phosphotriester groups [(Tp(R)Tp)2(CH2)5Acr 2bα; 2bβ (R = Et); cα, 2cβ (R = Me3C—CH2)] have been synthesized by the phosphotriester method in solution from each pure α and β isomers of the ethylated 5b or neopentylated 5c dinucleoside. This partial esterification of the phosphate groups stabilizes the nucleic acid chain against nucleolytic attack by P 1 and S 1 nucleases. This effect increases with the size of the alkyl groups. It also depends upon the steric configuration of the alkylphosphotriester groups: the β isomers are more resistant to S 1 nuclease than the a isomers. Tetrathymidylates bearing two “neopentyl” groups (Tp(CH,CMe3)Tp)2 (CH2)5Acr 2cα and 2cβ give specific complexes with poly r(A) and the β isomer 2c binds a little stronger than the tetrahymidylate (Tp)n (CH2)5 Acr. The neopentyl group is stable under the conditions required for the synthesi...