Oligonucleotide conjugates of Eu(III) tetraazamacrocycles with pendent alcohol and amide groups promote sequence-specific RNA cleavage

Eu(III) complexes of two neutral bifunctional tetraaaza macrocyclic ligands {1-[1-carboxamido-3-(4-nitrophenyl)propyl]-4,7,10-tris(2-hydroxyethyl)-1,4 ,7,10-tetraazacyclododecane and 2-(4-nitrobenzyl)-1,4,7,10-tetrakis (2-hydr oxyethyl)-1,4,7,10-tetraazacyclododecane} are prepared. Eu(III) complexes o f the isothiocyanate derivatives of these macrocycles are treated with olig onucleotides containing 2'-O-propylamine linkers to form conjugates. Hydrol ytic cleavage of an oligoribonucleotide is promoted by Eu(III) macrocyclic oligonucleotide conjugates containing complementary (antisense) sequences. Cleavage is not observed in the presence of Eu(III) conjugates containing s crambled sequences nor by free complex. Despite the fact that one of the fr ee macrocyclic complexes is more reactive than the other, the extent of cle avage observed is similar for conjugates containing either Eu(III) macrocyc lic complex.