A1 Refereed original research article in a scientific journal
Zn(2+) complexes of di- and tri-nucleating azacrown ligands as base-moiety-selective cleaving agents of RNA 3 ',5 '-phosphodiester bonds: Binding to guanine base
Authors: Wang Q, Leino E, Jancso A, Szilagyi I, Gajda T, Hietamaki E, Lonnberg H
Publisher: WILEY-BLACKWELL
Publication year: 2008
Journal:: ChemBioChem
Journal name in source: CHEMBIOCHEM
Journal acronym: CHEMBIOCHEM
Volume: 9
Issue: 11
First page : 1739
Last page: 1748
Number of pages: 10
ISSN: 1439-4227
DOI: https://doi.org/10.1002/cbic.200800095
Abstract
The ability of the dinuclear Zn(2+) complex of 1,4-bis[(1,5,9-triazacyclododecan-3-yloxy)methyl]benzene (L) to promote the cleavage of the phosphodiester bond of dinucleoside-3',5'-monophosphotes that contain a guanine base has been studied over a narrow pH range from pH 5.8 to 7.2 at 90 degrees C Comparative measurements have been carried out by Using the trinuclear Zn(2+) complex of 1,3,5-tris[(1,5,9-triazacyclododecon-3-yloxy)methyl]benzene (L(2)) as a cleaving agent and guanylyl-3',5'-guanosine (5'-GPG-3') as a substrate. The strength of the interaction between the cleaving agent and the starting material has been elucidated by UV spectrophotometric titrations. The speciation and binding mode have been clarified by potentiometric titrations with hydrolyticolly stable 2'-O-methylguanylyi-3',5'-guanosine and (1)H NMR spectroscopic measurements with guanylyl-3',5'-guanosine. The results show that the guanine base is able to serve as a site for anchoring for the Zn(2+)-azacrown moieties of the cleaving agents L(1) and L(2) analogously to uracil base. The interaction is, however, weaker than with the uracil base and, hence, only the 5'-GPG-3' site (in addition to 5'-GpU-3' and 5'-UpG-3' sites) is able to markedly modulate the phosphodiester cleavage by the 1 Zn(2+) complexes of di- and trinucleating azocrown ligands containing an ether oxygen as a potential H-bond-acceptor site.
The ability of the dinuclear Zn(2+) complex of 1,4-bis[(1,5,9-triazacyclododecan-3-yloxy)methyl]benzene (L) to promote the cleavage of the phosphodiester bond of dinucleoside-3',5'-monophosphotes that contain a guanine base has been studied over a narrow pH range from pH 5.8 to 7.2 at 90 degrees C Comparative measurements have been carried out by Using the trinuclear Zn(2+) complex of 1,3,5-tris[(1,5,9-triazacyclododecon-3-yloxy)methyl]benzene (L(2)) as a cleaving agent and guanylyl-3',5'-guanosine (5'-GPG-3') as a substrate. The strength of the interaction between the cleaving agent and the starting material has been elucidated by UV spectrophotometric titrations. The speciation and binding mode have been clarified by potentiometric titrations with hydrolyticolly stable 2'-O-methylguanylyi-3',5'-guanosine and (1)H NMR spectroscopic measurements with guanylyl-3',5'-guanosine. The results show that the guanine base is able to serve as a site for anchoring for the Zn(2+)-azacrown moieties of the cleaving agents L(1) and L(2) analogously to uracil base. The interaction is, however, weaker than with the uracil base and, hence, only the 5'-GPG-3' site (in addition to 5'-GpU-3' and 5'-UpG-3' sites) is able to markedly modulate the phosphodiester cleavage by the 1 Zn(2+) complexes of di- and trinucleating azocrown ligands containing an ether oxygen as a potential H-bond-acceptor site.
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