7-DEAZAADENOSINE - OLIGORIBONUCLEOTIDE BUILDING-BLOCK SYNTHESIS AND AUTOCATALYTIC HYDROLYSIS OF BASE-MODIFIED HAMMERHEAD RIBOZYMES

A 7-deazaadenosine (= tubercidin; c7A; 1) building block for solid-pha se oligoribonucleotide synthesis was prepared. The amino group of 1 wa s protected with the (dimethylamino)methylidene residue (-->3), and th e monomethoxytrityl group was introduced at OH-C(5') (-->4). Protectio n of OH-C(2') was carried out by silylation, showing that use of the ( i-Pr)3Si group resulted in high 2'-O-selectivity (-->5b, 80%). Reactio n of 5b with PCl3 afforded the phosphonate 7 which was used in solid-p hase oligoribonucleotide synthesis. The autocatalytic hydrolysis of ha mmerhead ribozymes using -C-C-C-U-U-C-G-G-G-G-A-C-U-C-U-G-A-A-G-A-G-G- C-G-C as substrate strand (S) and modified G-C-G-C-C-G-A-A-A-C-U-C-C-C as enzyme strand (E) was studied. When c7A replaced A13 or A14, a sma ll decrease of catalytic activity was observed, while modification in position A15 enhanced the autocatalytic hydrolysis. The results demons trate, that the atom N(7) of adenosine in any of these positions is no t crucial for ribozyme action.