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-hydroxyethyl)-1,4,7,10-tetraaza cyclododecane¿ are prepared. Eu(III) complexes of the isothiocyanate derivatives of these macrocycles are treated with oligonucleotides containing 2'-O-propyl-amine linkers to form conjugates. Hydrolytic 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 scrambled sequences nor by free complex. Despite the fact that one of the free macrocyclic complexes is more reactive than the other, the extent of cleavage observed is similar for conjugates containing either Eu(III) macrocyclic complex.
Huang
L
L
Department of Chemistry, State University of New York at Buffalo, Amherst 14260-3000, USA.
Chappell
L L
LL
Iranzo
O
O
Baker
B F
BF
Morrow
J R
JR
D000438:Alcohols / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D005063:Europium / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*
D000438:Alcohols; D000577:Amides; D006571:Heterocyclic Compounds; D009841:Oligonucleotides; D005063:Europium; D012313:RNA