Oligothymidylates covalently linked to an acridine derivative and with modified phosphodiester backbone: circular...

Oligothymidylates involving alternating alkyl phosphotriester-phosphodiester or methylphosphonate-phosphodiester backbones and covalently linked to an acridine derivative have been studied using circular dichroism. Two isomers with the same diastereoisomeric configuration for all the phosphotriesters (ethyl triester and neopentyl triester) or the methylphosphonate linkages were studied. These six compounds were compared to the parent oligonucleotide with unmodified phosphodiester bonds. Intramolecular interactions between the acridine and the bases of the oligonucleotides were revealed by the induced circular dichroism of the acridine dye. Binding to poly(rA) and poly(dA) induced large changes in the circular dichroism signal. All oligothymidylates formed double-stranded complexes with poly(rA). Substitution of phosphotriesters and methylphosphonates to phosphates allowed both double- and triple-stranded structures to be formed with with poly(dA). The double-stranded structures formed with poly(rA) and poly(dA) were characterized by different environments of the acridine dye. The circular dichroism spectra of the complexes with poly(dA) and the thermal stabilities of the complexes formed with both poly(rA) and poly(dA) were drastically dependent of the diastereoisomeric configuration of the phosphate modification. For the complexes formed with the pseudoequatorial stereoisomer the modification of the phosphate groups increased the stability of the complexes as compared with the oligothymidylate containing only phosphodiester linkages whereas it decreased it for pseudoaxial modifications.