Zn super(2+) 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

• Published in: Helvetica chimica acta Vol. 96; no. 1; pp. 31 - 43
• Main Authors: Niittymaeki, Teija, Burakova, Ekaterina, Laitinen, Evelina, Leisvuori, Anna, Virta, Pasi, Lonnberg, Harri
• Format: Journal Article
• Language: English
• Published: 01.01.2013
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.201200153

2-(3,5-Bis{[1,5,9-tris(trifluoroacetyl)-1,5,9-triazacyclododecan-3 -ylo xy]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)tetrah ydrofuran-2-yl]acetyl}amino)e thoxy]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 Zn super(2+)--bis(azacrown) complex and virtually abolished its selectivity towards the uridine sites.