site-selective artificial ribonucleases oligonucleotide conjugates containing multiple imidazole residues in the catalytic domainsite-selective人工核糖核酸酶寡核苷酸轭合物包含多个咪唑残留在催化领域.pdf

SAGE-Hindawi Access to Research Journal of Nucleic Acids Volume 2011, Article ID 748632, 17 pages doi:10.4061/2011/748632 Research Article Site-Selective Artificial Ribonucleases: Oligonucleotide Conjugates Containing Multiple Imidazole Residues in the Catalytic Domain Natalia G. Beloglazova,1 Martin M. Fabani,2 Nikolai N. Polushin,3 Vladimir V. Sil’nikov,1 Valentin V. Vlassov,1 Elena V. Bichenkova,2 and Marina A. Zenkova1 1 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia 2 School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, Manchester M13 9PL, UK 3 Fidelity Systems Inc., 7961 Cessna Avenue, Gaithersburg, MD 20879, USA Correspondence should be addressed to Marina A. Zenkova, marzen@niboch.nsc.ru Received 7 April 2011; Accepted 5 July 2011 Academic Editor: Dmitry A. Stetsenko Copyright © 2011 Natalia G. Beloglazova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Design of site-selective artificial ribonucleases (aRNases) is one of the most challenging tasks in RNA targeting. Here, we designed and studied oligonucleotide-based aRNases containing multiple imidazole residues in the catalytic part and systematically varied structure of cleaving constructs. We demonstrated that the ribonuclease activity of the conjugates is strongly affected by the number of imidazole residues in the catalytic part, the length of a linker between the catalytic imidazole groups of the construct and the oligonucleotide, and the type of anchor group, connecting linker structure and the oligonucleotide.