A1 Refereed original research article in a scientific journal
Zn2+ Complexes of 3,5-Bis[(1,5,9-triazacyclododecan-3-yloxy)methyl]phenyl Conjugates of Oligonucleotides as Artificial RNases: The Effect of Oligonucleotide Conjugation on Uridine Selectivity of the Cleaving Agent
Authors: Niittymaki T, Burakova E, Laitinen E, Leisvuori A, Virta P, Lonnberg H
Publisher: WILEY-V C H VERLAG GMBH
Publication year: 2013
Journal: Helvetica Chimica Acta
Journal acronym: HELV CHIM ACTA
Number in series: 1
Volume: 96
Issue: 1
First page : 31
Last page: 43
Number of pages: 13
ISSN: 0018-019X
DOI: https://doi.org/10.1002/hlca.201200153
Abstract
2-(3,5-Bis{[1,5,9-tris(trifluoroacetyl)-1,5,9-triazacyclododecan-3-yloxy]methyl}phenoxy)ethanol was synthesized and converted to a O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite building block, 12. 2'-O-Methyl oligoribonucleotides incorporating a 2-[(2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)ethyl 4-oxopentanoate or a 2-{2-[2-({[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]acetyl}amino)ethoxy]ethoxy}ethyl 4-oxopentanoate non-nucleosidic unit close to the 3'-terminus were assembled on a solid support, the 4-oxopentanoyl protecting groups were removed by treatment with hydrazinium acetate on-support, and 12 was coupled to the exposed OH function. The deprotected conjugates were purified by HPLC, and their ability to cleave a complementary RNA containing either uridine or some other nucleoside at the potential cleaving site was compared. Somewhat unexpectedly, conjugation to an oligonucleotide did not enhance the catalytic activity of the Zn2+?bis(azacrown) complex and virtually abolished its selectivity towards the uridine sites.
2-(3,5-Bis{[1,5,9-tris(trifluoroacetyl)-1,5,9-triazacyclododecan-3-yloxy]methyl}phenoxy)ethanol was synthesized and converted to a O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite building block, 12. 2'-O-Methyl oligoribonucleotides incorporating a 2-[(2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)ethyl 4-oxopentanoate or a 2-{2-[2-({[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]acetyl}amino)ethoxy]ethoxy}ethyl 4-oxopentanoate non-nucleosidic unit close to the 3'-terminus were assembled on a solid support, the 4-oxopentanoyl protecting groups were removed by treatment with hydrazinium acetate on-support, and 12 was coupled to the exposed OH function. The deprotected conjugates were purified by HPLC, and their ability to cleave a complementary RNA containing either uridine or some other nucleoside at the potential cleaving site was compared. Somewhat unexpectedly, conjugation to an oligonucleotide did not enhance the catalytic activity of the Zn2+?bis(azacrown) complex and virtually abolished its selectivity towards the uridine sites.
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