Di(azacrown) conjugates of 2'-O-methyl oligoribonucleotides as sequence-selective artificial ribonucleases.
Functionalized 2'-O-methyl oligoribonucleotides bearing two 3-(3-hydroxypropyl)-1,5,9-triazacyclododecane ligands attached via a phosphodiester linkage to a single non-nucleosidic building block have been prepared on a solid-support by conventional phosphoramidite chemistry. The branching units employed for the purpose include 2,2-bis(3-hydroxypropylaminocarbonyl)propane-1,3-diol, 2-hydroxyethyl 3'-O-(2-hydroxyethyl)-beta-D-ribofuranoside, and 2-hydroxyethyl 2'-O-(2-hydroxyethyl)-beta-D-ribofuranoside. Each of these has been introduced as a phosphoramidite reagent either into the penultimate 3'-terminal site or in the middle of the oligonucleotide chain. The dinuclear Zn2+ complexes of these conjugates have been shown to exhibit enhanced catalytic activity over their monofunctionalized counterpart, the 3'-terminal conjugate derived from 2-hydroxyethyl 3'-O-(2-hydroxyethyl)-beta-D-ribofuranoside being the most efficient cleaving agent. This conjugate cleaves an oligoribonucleotide target at a single phosphodiester bond and shows turnover and 1000-fold cleaving activity compared to the free monomeric Zn2+ chelate of 1,5,9-triazacyclododecane.
Niittymäki
Teija
T
Department of Chemistry, University of Turku, FIN-20014 Turku, Finland.
Virta
Pasi
P
Ketomäki
Kaisa
K
Lönnberg
Harri
H
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000378:metabolism; D001483:Base Sequence; D002384:Catalysis; D043822:Cyclodecanes / Q000737:chemistry*; D008024:Ligands; D008745:Methylation; D008956:Models, Chemical; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism; D010755:Organophosphates / Q000737:chemistry*; D012260:Ribonucleases / Q000138:chemical synthesis*; D013997:Time Factors; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
D001372:Aza Compounds; D043822:Cyclodecanes; D008024:Ligands; D009843:Oligoribonucleotides; D009942:Organometallic Compounds; D010755:Organophosphates; D012260:Ribonucleases; D015032:Zinc