Oligodeoxyribonucleotide Phosphotriesters

The common interest in the synthesis of oligo(nucleoside O -alkyl phosphates) was posed first by the generally accepted view that alkylation of DNA by several alkylating agents may also occur at internucleotide phosphate nonbridging oxygen atom(s) inducing DNA misfunction (1 ). Perturbations in backbone conformation, partial charge neutralization of the backbone, and steric interference by the esterifying alkyl groups on the protein-nucleic acid interactions were all proposed to explain changes in the DNA biochemistry on phosphate alkylation (2 ). Thus, the availability of synthetic “DNA-triesters” as models for studying stability of the phosphate-alkylated DNA fragments under the physiological conditions became a challenging task for oligonucleotide chemists. Furthermore, recent increasing interest in antisense oligonucleotide analogs (3a , 3b ) brought the additional impact to development of reliable technology of the synthesis of oligonucleotide phosphotriesters.