IMIDAZOLE TETHERED OLIGODEOXYRIBONUCLEOTIDES - SYNTHESIS AND RNA CLEAVING ACTIVITY

A solid support (3) and a non-nucleosidic phosphoramidite building blo ck (4), both containing a thioester bond is their structure, were synt hesized. They were used in the preparation of oligonucleotides tethere d to an imidazole group at their 3'- or 5'-terminus, as well as at the 1'-position of nonterminal 3'-deoxypsicothymidine units. The desired functional groups were introduced during the deprotection of the oligo nucleotide by using the primary amino group of histamine or 1-(3-amino propyl)imidazole as a nucleophile. The ability of the tethered oligonu cleotides to hydrolyze complementary RNA strands was tested. Of the ol igonucleotides prepared, 12b, bearing a histamine group at the 3'-end, was shown to promote a sequence specific strand scission of RNA in th e presence of Zn2+ ions.