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

Synthesis of di-, TT tri-, T*T*T, and tetrameric, T*T*T*T, building b locks with carbamate internucleoside linkage, =3'-NH-CO-O-5', was ach ieved by the reaction of mono-, di-, or trimeric nucleoside 5'-O-p-nit rophenyl carbonate intermediates with 3'-amino-3'-deoxythymidine. Thes e 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 deriv ed therefrom have been studied for their binding properties to complem entary nucleic acids and for their nuclease sensitivity. Oligonucleoti des containing one, two, or three carbamate linkages at 3'-end were fo und to have increased nuclease resistance and did not effect the duple x stability significantly.