A Guide to the Russian Academy of Sciences - University of Texas ...

the Department of Mathematics of Moscow State university in 1971 and joined the
institute as a postgraduate student that same year, defended his thesis on the
conformational possibilities of irregular sites of DNA in 1980. His main interests
are in conformational analysis and the sequencing by hybridization. The institute
has, in the last few years, developed new research groupings of its scientists to
solve major scientific problems.
1997 update: THE HUMAN GENOME STRUCTURE INFORMATION
CENTER Head Yuri P. Lysov, Ph.D., D.Sc.
The investigations on the nucleic acid structure continued. At the same time the work was
concentrated on developing the programs to support biological data-processing
supply under the Russian National Human Genome Program. Additional means
were created to form compressed databases and procedures for quick access to and
analysis of information present in these databases. The works on development of a
method for sequencing by hybridization with an oligonucleotide matrix continued.
A detailed study of the stacking hybridization usage for the probe effective length
increase was carried out to obtain information about the DNA regions under
investigation. If an octanucleotide matrix is used for stacking hybridization,
pentanucleotides may help in sequencing DNA regions of several thousand
nucleotides in length. The limits of the method application for different lengths of
immobilized oligonucleotides are determined. We are studying the method
effectivity for stacking hybridization on a matrix containing oligonucleotides with
the internal degeneration regions able to form duplexes of a random base sequence
at these regions. We have proposed an increase of sequencing effectivity by
measuring several distances between regions of the fragment under investigation.
Such procedure makes possible an unambiguous reconstruction of the fragments
even in the presence of internal repeats. The works on creation and improvement of
equipment for luminescent monitoring the hybridization with an oligonucleotide
matrix are in progress. Necessary mathematical and program supports are
developed. The results obtained were presented at different international and
Russian conferences.
1997 update: PROTEIN-DNA RECOGNITION
Head Georgii V. Gurskii, Ph.D., D.Sc.
A search of new structural motifs to design the sequence-specific DNA-binding and DNAcleaving
ligands was carried out using computer modelling, synthesis of new
compounds, and DNA-binding studies. The new type synthetic elongated DNAbinding
ligands composed of N,4-substituted mono- and diphthalimide units and
containing positively charged groups at both ends of the molecules were
synthesized. These ligands exhibit fluorescence at 460 nm upon excitation at 340
nm. The ligand incorporating a phthalimide fragment connected by a flexible chain
to a dipyrrolcarboxamide group upon binding is localized in the DNA narrow
groove and covers 5 base pairs. If a ligand consists of phthalimide fragments only
then no binding in the narrow DNA groove occurs. In this case a slightly
fluorescent outside binding type of the complex is formed which is saturated when
one ligand molecule is bound per two base pairs. An unusual 3:1 stoichiometry for
a complex formed by elongated bis-netropsins and their binding sites on DNA was
observed. CD measurements revealed two types of bis-netropsin complexes with
poly[d(A-T)].poly[d(A-T)]. The first is characterized by 1:1 saturation ratio of
bound ligand molecules per 10 base pairs. The cooperative binding of two
additional bis-netropsin molecules to the first type of the complex results in the
second type complex formation. Unlike the results obtained for binding to
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