SOME RECENT FINDINGS IN THE BIOTECHNOLOGY OF BIOLOGICALLY IMPORTANT NUCLEOSIDES

63 Nucleosides embrace a large family of natural and chemically modified analogues of great structural diversity and a broad spect rum of biological activity. Analogues of natu ral nucleosides as well as nucleoside antibio tics belong to the most important classes of antiviral drugs, and they are extensively used in the treatment of a variety of cancers. Base and sugar modified nucleosides are very valuab le constituents of artificial oligonucleo tides of medicinal potential making these oligomers more stable in biological fluids and improving their targeting proper-ties. The chemistry of many antiviral and anticancer drugs, as well as building blocks for oligonucleotide synthesis remains a challenging problem resulting in a high price of the desired compounds preventing them from extensive therapeutic application and use in oligonucleotide business (for a recent reviews, see [1–3]. Analysis of the state of the art of chemoenzymatic synthesis of nucleosides led us to conclusion that the chemo-enzymatic methodo logy demonstrates a number of advantages over the chemical methods of nucleoside synthesis, viz., high total yield of desired pro ducts, simplicity of work-up of reaction mixtur es and isolation of products, conform to the principles of «green chemistry» to a greater extent vs. the fine organic synthesis [1–3]. Up to the present, a vast majority of the modified nucleosides have been synthesized by chemical methods. Despite the impressive progress achieved in the development of chemical methods, production of many antiviral and anticancer drugs, as well as other biologically active compounds remains a challenge. This leads to high drug costs and, therefore, prevents extensive biological trials and studies, as well as a wide therapeutic application. The need for the development of new strategies became apparent in the late 1970s. The chemo-enzymatic (biotechnological) strategies are currently displacing multi-stage chemical processes, and this allows perfor ming the key transformations with high selectivity and regioand stereo-specificity. Considerable progress in the production of biologically important analogs of natural nucleosides has been achieved through the rational combination of chemical and biochemical transformations. Use of recombinant nucleoside phosphorylases (NPs) and N-deoxyribosyl transferases (NDTs) as biocatalysts for the synthesis of natural nucleosides and their modified analogs is of considerable importance UDK 577.113.3