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

Abstract

Building blocks derived from 7-deazaguanosine (c7G, 1) were prepared for 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 studied with regard to regioselectivity. It was found that the triisopropylsilyl group in combination with the (dimethylamino)methylidene residue gave the highest 2'-selectivity (--> 5e). The 2'-O-silyl derivative 5e was reacted with PCl3 affording the 3'-phosphonate 7 which was used in solid-phase oligoribonucleotide synthesis. Oligonucleotides derived from U-G-G-G-G-U with an increasing number of c7G residues instead of G were synthesized. Aggregation was studied by polyacrylamide-gel electrophoresis and CD spectroscopy. Disaggregation of the G4-Structure of U-G-G-G-G-U was observed when c7G replaced G, demonstrating that guanine N(7) participates in the aggregation process.