(AMINOMETHYL)PHOSPHONATE DERIVATIVES OF OLIGONUCLEOTIDES

Oligothymidylate (aminomethyl)phosphonates have been prepared, and the ir enzymatic and physicochemical properties have been studied. The ind ividual isomers of the protected dimers have been separated, character ized, and incorporated into oligonucleotides in which the backbone con sists of alternating (aminomethyl)phosphonate and phosphodiester linka ges. One of these net neutral, single isomer oligonucleotides forms a duplex with its complementary sequence which is more stable than the c orresponding natural counterpart, whereas the other isomer is consider ably less stable. Specificity of hybridization is maintained, as deter mined by the reduction in melting temperature observed upon the introd uction of mismatches into the complementary strand of the duplex. The (aminomethyl)phosphonate linkage is stable toward enzymatic degradatio n but can be hydrolyzed in aqueous solution at elevated temperature.