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Biologically important modified oligonucleotides with increased stability towards nucleases and phosphodiesterases

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This project is a sequel to the previous collaborative research programmes between the laboratories for the synthesis of modified oligonucleotides (ONs) of biological importance with improved stability towards cell enzymes. In continuation of the work on the preparation of biologically active 2'-5'-oligoadenylate derivatives several new analogues with promising antiviral and anticancer activity have been prepared. Further development of related 2-5A analogs may provide specific compounds for chemotherapy and chemoprevention. During the course of this work more than 100 new nucleoside, nucleotide and ON derivatives were prepared, their structure and conformational properties were investigated using different physico-chemical methods, such as UV,CD, X-ray and NMR spectroscopy. Developed for the first time was the preparation of ON derivatives with regiospecifically incorporated dialdehyde reactive groups and their successful use as affinity labels for restriction endonucleases and DNA methyltransferases. The developed methodology is of general importance and such ON analogues may be used not only for selective inhibition and affinity labelling but also for a covalent attachment of different anchor groups to ONs such as fluorescent, radioactive, and so on. The scientific results of this project were presented at five international meetings, 16 papers were published in international journals.

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