Projects / Programmes
Chemistry and structure of biologically active compounds
January 1, 2004
- December 31, 2008
| Code |
Science |
Field |
Subfield |
| 1.04.00 |
Natural sciences and mathematics |
Chemistry |
|
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| Code |
Science |
Field |
| P390 |
Natural sciences and mathematics |
Organic chemistry |
chiral molecules, asymmetric synthesis, chiral catalysts, NMR spectroscopy, structure, conformation, oligonucleotides, G-quadruplex, RNA interference
Researchers (14)
Organisations (2)
Abstract
The research program represents a synergy of activities and plans of two research groups- synthetic and structural, and includes synthesis of biologically active compounds and new synthetic approaches for their preparation as well as exploration of their structure. One part of research consists of studying of catalytic transformations, synthesis of new ligands and their metal complexes (catalysts). Our main interest is in the development of catalysts for two industrially important synthetic transformations: asymmetric reductions and C-C bond formation. Such transformations are commonly used in the synthesis of biologically active compounds and can also be used in the synthesis of modified oligonucleosides. NMR spectroscopy will be a useful tool in structure elucidation of catalysts and intermediates as well as in the studies of reaction mechanisms with purpose to improve synthetic techniques. Second part of research activities involves chemical identification and conformational studies as well as 3D structure determination. Knowledge of 3D structure can contribute to our understanding of the roles of nucleic acids such as guanine-quadruplexes and short synthetic RNA molecules which have been shown to silence particular gene through RNA interference. 3D structure and insight into intermolecular interactions with atomic resolution are very useful for prediction, interpretation, modification and design of their functions.
Significance for science
Efficient catalysts for better, simpler and economically interesting synthetic procedures were developed that lead to less side products and less waste. Studies of reaction mechanisms have improved understanding of catalytic processes and contributed to progress in catalytic properties. Results of our structural studies of G-quadruplexes have contributed to understanding of their structure and dynamics. We have discovered new structural motifs. Such knowledge is important in design of selective ligands that stabilize G-quadruplex structure and thus represent potential drugs for treatment of cancer. Understanding of G-quadruplex formation and role of cations in the process is important in the design of nanodevices, whereas knowledge of cation movement is significant in design of electric conductivity of nanowires and in development of artificial ion channels. Structural work on miRNA:mRNA constructs and their interactions with proteins enable determination of structural motifs which are important for activity of miRNA. New knowledge will contribute to novel applications in medical treatment of cancer, diabetes, hearth problems, etc. Before miRNA therapy can be used in humans, molecule has to be efficiently and selectively transfered to target site in human body. Acquisiton of NMR data is critical, the most time consuming and expensive step in structural determination of proteins. Our approach towards unconventional sampling of evolution time space in acquisition of multidimensional spectra is based on random sampling, which is followed by Fourier transform. NMR methods based on random sampling simultaneously offer new data which can be used in structure calculations. The use of random sampling in NMR spectroscopy enables acquisition of spectra with high resolution in indirectly sampled dimensions of multidimensional spectra. In the case of 3D HNCO experiment with CA couplings the method has shown to be applicable to obtain six one-, two- and three–main chain related scalar couplings which can be used in structure calculations. Among them we can use 2JNCa(i-1) coupling which is highly dependent on conformation of protein backbone and gives information about secondary structure in early stages of structure calculation. Our experiments show great potential in measurement of residual diplar couplings which are important in high-resolution structure determination. We expect that our method will speed up NMR data acqusiton and at the same time enable study of protein samples with more accurate results.
Significance for the country
We are the only group in Slovenia which focuses on novel synthetic approaches in the field of asymmetric catalysis which is relatively young (30 years) and complex branch of organic chemistry. Interest of pharmaceutical industry for such technologies is rising. We are actively cooperating with two local pharmaceutical companies. Students of chemistry are introduced into the field of asymetric catalysis which is only briefly presented during the courses. Research within the program group will contribute new knowledge in the field of NMR spectroscopy. NMR spectroscopy is used in structural studies and in studies of conformational problems of small molecules including organic molecules, which are active ingredients of drugs and macromolecules such as proteins and nucleic acids. We expect that our results will contribute to wideing and deepening of expertise in the field of NRM spectroscopy in Slovenia. Our studies contribute towards development of new scientific fields in priority areas of Slovenia. New knowledge about structures of DNA quadruplexes and miRNA:mRNA complexes will be important in development of novel anticancer and antiviral drugs. This will be of special interest for pharmaceutical industry and consequently for public health in Slovenia. Obtained results will contribute to increase in higly cited publication in international journals. Our studies are subject of several diploma and doctoral thesis.
Most important scientific results
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Most important socioeconomically and culturally relevant results
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