SYNTHESIS OF DIMERIC, TRIMERIC, AND TETRAMERIC BUILDING-BLOCKS WITH NOVEL CARBAMATE INTERNUCLEOSIDE LINKAGES AND THEIR INCORPORATION INTO OLIGONUCLEOTIDES

Synthesis of di-, T*T tri-, T*T*T, and tetrameric, T*T*T*T, building blocks with carbamate internucleoside linkage, *=3'-NH-CO-O-5', was achieved by the reaction of mono-, di-, or trimeric nucleoside 5'-O-p-nitrophenyl carbonate intermediates with 3'-amino-3'-deoxythymidine. These building blocks were suitably protected at 5'-position and converted into phosphoramidites, or attached onto CPG, and then used for the ''chimeric oligonucleotide'' synthesis. The novel oligonucleotides derived therefrom have been studied for their binding properties to complementary nucleic acids and for their nuclease sensitivity. Oligonucleotides containing one, two, or three carbamate linkages at 3'-end were found to have increased nuclease resistance and did not effect the duplex stability significantly.