7-Deazaadenosine: Oligoribonucleotide Building Block Synthesis and Autocatalytic Hydrolysis of Base-Modified Hammerhead Ribozymes

Article abstract of DOI:10.1002/hlca.19930760502

A 7-deazaadenosine ( = tubercidin; c⁷A; 1) building block for solid phase oligoribonucleotide synthesis was prepared.The amino group of 1 was protected with the (dimethylamino)methylidene residue (->3), and the monomethoxytrityl group was introduced at OH-C(5') (->4).Protection 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, 80percent).Reaction of 5b with PCl3 afforded the phosphonate 7 wich was used in solid-phase oligoribonucleotide synthesis.The autocatalytic hydrolysis of hammerhead ribozymes using pG-G-G-A-G-U-C-A-G-U-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 small decrease of catalytic activity was observed, while modification in position A¹⁵ enhanced the autocatalytic hydrolysis.The results demonstrate, that the atom N(7) of adenosine in any of these positions is not crucial for ribozyme action.