ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
KL20. Base and Sequence Selective Cleavage of Rna Phosphodiester Bonds
by Zn(II) Azacrown Chelates
H. Lönnberg a , Q. Wang a , P. Poijärvi-Virta a , K. Ketomäki a , M. Mannila a , T. Niittymäki a ,
P. Virta a , E. Leino a , A. Jancsó, b I. Szilágyi b , T. Gajda b
a Department of Chemistry, University of Turku, Vatselankatu 2, FIN-20014, Turku, Finland,
b Department of Inorganic and Analytical Chemistry, University of Szeged, P.O. Box 440, Szeged H-6720,
Hungary
e-mail: harlon@utu.fi
Many of the enzymes catalyzing phosphoryl transfer reactions contain Zn(II) in their catalytic center.[1] For this
reason, Zn(II)-based cleaving agents have received exceptionally wide interest among researchers attempting to
create chemical models for the enzyme action [2] and developing artificial restriction enzymes.[3] Among
various Zn(II) complexes, the azacrowns chekates exhibit two interesting properties: they promote the cleavage
of RNA phosphodiester bonds [4] and undergo selective binding to nucleic acid bases [5]. The affinity to uracil
and thymine bases is much higher than to guanine base, and adenine and cytidine bases are not recognized at
all. The binding of di- and tri-nuclear Zn(II) azacrown chelates to contiguous bases in a nucleic acid strand is a
co-operative process. The stability of the resultinh ternary complexes may, in fact, be so high that the complex
formation is possible at intracellular concentrations of Zn(II) ion. Various di- and tri-nucleating azacrown
ligands have been prepared and studied as base-selective cleaving agents of RNA using dinucleoside 3´, 5´monophosphates
and short synthetic oligoribonucleotides as model compounds [6-8]. Sequence-selective
artificial ribonucleases have, in turn, been obtained by tethering azacrown ligands to a 2´-O-methyl
oligoribonucleotide that recognizes the target sequence [9, 10]. The results of these studies are surveyed.
References:
[1] For a recent review, see Weston, J. (2005) Chem. Rev. 105, 2151.
[2] Mancin, F., Tecilla, P. (2007) New J. Chem. 31, 800.
[3] Niittymäki, T., Lönnberg, H. (2006) Org. Biomol. Chem. 4, 15.
[4] Kuusela, S., Lönnberg, H. (1994) J. Chem. Soc. Perkin Trans. 2, 2301.
[5] Aoki, S., Kimura, E. (2004) Chem. Rev. 104, 769.
[6] Wang, Q., Mikkola, S., Lönnberg, H. (2004) Chem. Biodiv. 1, 1316.
[7] Wang, Q., Lönnberg, H. (2006) J. Am. Chem. Soc. 128, 10716.
[8] Wang, Q., Leino, E, Jancsó, A., Szilágyi, I., Gajda, T., Hietamäki, E., Lönnberg, H. (2008) ChemBioChem,
in press.
[9] Niittymäki, T., Lönnberg, H. (2004) Bioconjugate Chem. 15, 1275.
[10] Niittymäki, T., Virta, P., Ketomäki, K., Lönnberg, H. (2007) Bioconjugate Chem. 18, 1583.
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