Achievements [Институт химической биологии и фундаментальной медицины]
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Laying the foundations targeted modification of genetic structures

Implementing targeted impact on genetic material, i.e. DNA and RNA, is one of the main challenge of molecular biology and pharmacology

It were siberian researchers N. Grineva and D. Knorre, that in 60s the world's first had formulated the principle of targeted impact on nucleic acids with oligonucleotides carring reactive groupes.
Such nucleotide conjugates, when bound to complementary DNA/RNA sequences, deliver reactive group capable of damaging in certain nucleic acids sites.
Siberian researchers studies had proved possibility of targeted impact on DNA and RNA. Various reactive reagents to modify heterocyclic bases of nucleic acids were synthetised in ICBFM.
The findings had offered the prospect of a new generation of antiviral drugs and drugs to damage the genetic material of cells to undergo a malignant transformation.
The studies had been far ahead of such work abroad.
A new section of physico-chemical biology, which was bioorganic chemistry of nucleic acid duplexes, had been created with the indisputable Russian priority.

D. Knorre - academician,
N. Grineva - D.Sc.,
R. Salganik - Corresponding Member of USSR Academy of Sciences, Professor,
Z. Shabarova - D.Sc., Prof.
Lenin Prize in 1990.

Oligonucleotide derivatives are biologically active compounds and research tools for protein-nucleic acid interactions

ICBFM scientists had solved the problem of creating new types of biologically active substances, i.e. a new generation of therapeutic drugs with gene-directed action, and had designed methods to study the nucleoprotein complexes structure and to study of protein-nucleic acid interactions with reactive oligonucleotide derivatives as well.
As a result of this work unique data about the ribosomal functional centers structure for bacteria and human had been obtained; cell-surface receptors to interact with nucleic acids had been discovered, and it was shown that the oligonucleotides had bound to the cellular receptor CD4 to block the infection of cells by HIV-1; it was found that nucleic acids reacted with immunoglobulins and growth factors in the blood stream; new approaches to analyze protein-nucleic acids interaction for the enzymes of replication, repairation, topoisomerisation and restriction had been proposed.
Developed reagents and methods have been used in Russian and foreign research centers and businesses.
The results are both of fundamental and practical importance in connection with the creation of new potential therapies based on nucleic acids and oligonucleotides. These studies laid the foundation for the development of a new direction of molecular pharmacology.

A. Veniaminova, Ph.D.,
V. Vlasov, Academician,
M. Graifer, D.Sc.,
V. Zarytova, D.Sc.,
E. Ivanova, Ph.D.,
G. Karpova, D.Sc.,
G. Nevinsky, D.Sc.,
L. Yakubov, Ph.D.
State Prize of the Russian Federation in the field of science and technology in 1999.

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