7-DEAZAGUANOSINE - SYNTHESIS OF AN OLIGORIBONUCLEOTIDE BUILDING-BLOCKAND DISAGGREGATION OF THE U-G-G-G-G-U G4 STRUCTURE BY THE MODIFIED BASE

Building blocks derived from 7-deazaguanosine (c7G, 1) were prepared f or solid-phase oligoribonucleotide synthesis. Compound 1 was converted into the isobutyryl derivative 2b and the (dimethylamino)methylidene compound 3 (Scheme 1). After tritylation (--> 4a, b), silylation was s tudied with regard to regioselectivity. It was found that the triisopr opylsilyl group in combination with the (dimethylamino)methylidene res idue gave the highest 2'-selectivity (--> 5e). The 2'-O-silyl derivati ve 5e was reacted with PCl3 affording the 3'-phosphonate 7 which was u sed in solid-phase oligoribonucleotide synthesis. Oligonucleotides der ived from U-G-G-G-G-U with an increasing number of c7G residues instea d of G were synthesized. Aggregation was studied by polyacrylamide-gel electrophoresis and CD spectroscopy. Disaggregation of the G4-Structu re of U-G-G-G-G-U was observed when c7G replaced G, demonstrating that guanine N(7) participates in the aggregation process.