Dubey I. Chemical modification of oligonucleotides and synthesis of their conjugates

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0508U000489

Applicant for

Specialization

  • 02.00.10 - Біоорганічна хімія

26-09-2008

Specialized Academic Board

Д 26.220.01

V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine

Essay

Synthetic oligonucleotides, their conjugates and analogues. Development of a complex of new methods of chemical updating synthetic oligonucleotides and obtaining their conjugates with molecules of various classes and studying of physical, chemical and biological properties modified oligonucleotides. Chemical synthesis, a highly effective liquid chromatography, TLC, gel-electrophoresis, spectroscopy, NMR-spectrometry. New polymer supports for the synthesis of natural and modified oligonucleotides, H-phosphonate and phosphitamide reagents for oligonucleotide functionalization and attachment of reporter molecules have been proposed. Efficient methods of the preparation of oligonucleotide conjugates with fluorescein, imidazo[4,5-b]phenazine, cationic porphyrins and their metalocomplexes, and 1,4,7-triazacyclonionane, have been developed. Triple hybrids of fluorescently labeled oligonucleotides with metaloporphyrin and transport peptide have been obtained. The structures of some labile products of DNA cleavage by chemical nucleases have been established and methods of their detection have been proposed. Biological activity of (2'-5')-oligoadenylates and modified antisignature oligonucleotides has been studied. Sphere of use - bioorganic chemistry.

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