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Projects / Programmes source: ARIS

Chemistry and structure of biologically active compounds

Periods
Research activity

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
P003  Natural sciences and mathematics  Chemistry 

Code Science Field
1.04  Natural Sciences  Chemical sciences 
Keywords
Structure, dynamics, DNA, RNA, proteins, NMR, asymmetric synthesis, catalyst, natural substance, folding, preorganization
Evaluation (rules)
source: COBISS
Researchers (28)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  53434  Stase Bielskute    Technical associate  2019 - 2020 
2.  36419  PhD Jasna Brčić  Chemistry  Researcher  2015 - 2019  36 
3.  24448  PhD Mirko Cevec  Biochemistry and molecular biology  Researcher  2015 - 2021  67 
4.  37459  PhD Andrej Emanuel Cotman  Chemistry  Junior researcher  2015 - 2018  61 
5.  31950  PhD Petra Galer  Chemistry  Researcher  2015 - 2017  27 
6.  26334  PhD Gregor Ilc  Biochemistry and molecular biology  Researcher  2018 - 2019  94 
7.  33235  PhD Andrea Kišić  Chemistry  Researcher  2015 
8.  35144  PhD Vojč Kocman  Chemistry  Researcher  2015 - 2021  47 
9.  17916  PhD Iztok Jože Košir  Chemistry  Researcher  2015 - 2021  558 
10.  38338  PhD Anita Kotar  Chemistry  Researcher  2021  57 
11.  32112  PhD Martina Lenarčič Živković  Biochemistry and molecular biology  Researcher  2015 - 2021  61 
12.  24975  PhD Damjan Makuc  Chemistry  Researcher  2015 - 2021  133 
13.  34525  PhD Maja Marušič  Chemistry  Researcher  2015 - 2021  53 
14.  12832  PhD Barbara Mohar  Chemistry  Researcher  2015 - 2018  113 
15.  53606  PhD Aleš Novotny  Chemistry  Junior researcher  2019 - 2021  16 
16.  37419  PhD Miha Ocvirk  Plant production  Researcher  2015 - 2020  178 
17.  50216  PhD Maria Orehova  Chemistry  Researcher  2019 - 2021  20 
18.  50619  PhD Daša Pavc  Chemistry  Junior researcher  2017 - 2021  20 
19.  52245  Katerina Peterkova  Chemistry  Technical associate  2021  12 
20.  10082  PhD Janez Plavec  Chemistry  Head  2015 - 2021  1,272 
21.  28022  PhD Peter Podbevšek  Chemistry  Researcher  2015 - 2021  119 
22.  38253  PhD Gašper Poklukar  Chemistry  Junior researcher  2015 - 2020 
23.  35062  PhD Tanja Potočnik  Plant production  Junior researcher  2015 - 2018  25 
24.  33237  PhD Slavko Rast  Chemistry  Researcher  2015 
25.  53547  PhD Ksenija Rutnik  Chemistry  Junior researcher  2019 - 2021  28 
26.  37460  PhD Urška Slapšak  Biochemistry and molecular biology  Junior researcher  2015 - 2019  23 
27.  22575  PhD Primož Šket  Chemistry  Researcher  2015 - 2021  222 
28.  30845  PhD Marko Trajkovski  Biochemistry and molecular biology  Researcher  2016 - 2021  61 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,261 
2.  0416  Slovenian Institute of Hop Research and Brewing  Žalec  5051762000  4,279 
Abstract
The research program combines activities of three research groups in areas of structure and dynamics of (bio)(macro)molecules, NMR method development, soluble metal complex-catalyzed energy efficient and low-waste asymmetric organic transformations and natural products. Understanding the roles of nucleic acids and proteins in living organisms requires insights into intricate relationships between their biological function and structure. NMR is an excellent tool for studies of structure and conformational changes of DNA, RNA and proteins as well as their interactions with ligands and cations under conditions which are close to physiological states. Guanine-rich DNA and RNA sequences have been shown to form G-quadruplexes. They are frequent in telomeric ends, in promoters of oncogenes and have also been utilized as nanodevices and as artificial ion channels in lipid bilayers. Our research in asymmetric synthesis relates to catalyzed asymmetric transformations, in particular to asymmetric reductions, to access chiral acids, esters, alcohols, amines, etc encountered as main components, for example, of drugs and food additives. The objective is to design easily made chiral catalysts with improved properties which can operate under mild reaction conditions and possess wide applications. Modern analytical methods enable insight into composition and identity of compounds in various medicinal and aromatic plants which represent an important source of potential drugs for the treatment or mitigation of various health problems.
Significance for science
Expected results of our research will help to broaden and deepen knowledge of structures and folding of DNA, RNA and proteins involved in several important biological processes as well as their mutual interactions and interactions with small molecules and cations. Understanding of processes in living organisms is based on knowledge of the relationship between structure and function, which recently also includes knowledge of the dynamic properties of molecules. Here, we accentuate the power of NMR in providing information on conformatial exchange and dynamic processes across a large span of time-scales. So far, very little is known about the structural motifs of G-quadruplex structures, which are taken up by guanine-rich regions in the promoter regions of oncogenes. Such knowledge is important for the understanding of the regulation of gene expression and in the design of new organic molecules, which can specifically stabilize a particular G-quadruplex structure. Novel ligands will help in the fight against various forms of cancer and many viral diseases.   Novel media for determination of RDC coupling constants are expected to extend possibilities for a partial alignment of small organic molecules and contribute to determination of stereochemistry is systems with chiral centers. So far, anisotropic media created by assembly of G-quartet based systems and G-quadruplexes forming liquid crystalline media have been exploited poorly. New methods will facilitate studies of complex biological mixtures, such as metabolites or peptidoglycans.   Up till now, very little is known about structural features of G-quadruplexes, which are made of guanine and cytosine residues only, as well as hybrid DNA:RNA quadruplexes. New data on pre-folded structures and new quadruplex structural features is important for the design of new organic molecules that could specifically stabilize certain G-quadruplex structure or its preorganized form and thus help in fight against various forms of cancer, many viral diseases, frontotemporal dementia and amyotrophic lateral sclerosis. We will also contribute to the development of experimental methods for oligonucleotide structure elucidation. A strong correlation between RNA G-quadruplex structures and their biological activity is expected to be developed. Results of our studies will uncover biological relevance of RNA G-quadruplexes and help in the design stage of new selective ligands for G-quadruplex stabilization and development of potential anti-cancer drugs.   Onset and prolongation of amyloid neuronal diseases (Parkinson's disease, Alzheimer's disease, Transmissible spongiform encephalopathy, etc.) still represent an unsolved problem. In further studies we hope to contribute to understanding of prion protein conversion into amyloid deposits and transfer knowledge to other models of amyloid diseases.   We are going to develop new efficient catalysts for better, simpler and economically more efficient processes, where less by-products and waste materials are produced. Study of reaction mechanisms of catalysis will contribute to better understanding of catalytic processes and will improve properties of catalysts. Development of efficient chiral ligands and catalysts to be used in asymmetric synthetic transformations is of the top interest for academic and industrial laboratories all over the world.   Knowledge about the identity and composition of bioactive substances in the tissues of medicinal plants will enable their further studies towards finding their natural resources. At the same time, identification of compounds gives a starting point for further research on their effectiveness and possible use. In the case of use of hops in brewing, the obtained information will help to understand hops role in the persistence and stability of beer, as is already known that it is a component, which plays a decisive role.
Significance for the country
Research within the program group P1-242 represents an important part of the activities of the Slovenian NMR Centre, which as a core partner of the EN-FIST Centre of Excellence connects academic users and industrial partners. New NMR methods will be available to the widest range of users. NMR spectroscopy is being extensively used to solve both structural and conformational problems of smaller molecules, including organic compounds, active pharmaceutical ingredients and macromolecules such as proteins, nucleic acids and carbohydrates. We expect to contribute to the dissemination and expansion of knowledge in the field of modern NMR spectroscopy to the broader Slovenian scientific community. We wish to emphasize our long-standing collaboration with pharmaceutical and chemical companies in Slovenia, particularly Krka, Lek, Helios, Bia Separations, Melamin and FerroČrtalič.   Novel NMR methods for partial allignment and RDC meassurements could be used in pharmaceutical and chemical industry in determination of relative stereochemistry. Structural, conformational and stereochemical features of molecules of natural origin and potential active pharmaceutical ingredients could be studied by means of NMR spectroscopy.   The search for correlations between the structure and function is highly relevant for pharmaceutical industry. We expect that our results will contribute to the understanding of various structural features of DNA, RNA and hybrid DNA:RNA quadruplex structures as well as their pre-folded forms. These systems could be used as targets for development of new drugs as well as in the design of nanomachines based on dynamic folding of oligonucleotides.   The results of our studies will be very important for the future determination of NMR solution-state RNA G-quadruplex structures. Furthermore, studies of binding interfaces will help to explain possible roles of RNA G-quadruplexes and will be attractive for pharmaceutical companies since we will focus on RNA G-quadruplexes located in the 5’-UTRs of certain mRNAs involved also in cancer.   By identifying structural anomalies of prion protein, we hope to better understand the initial stages of transmissible spongiform encephalopathy and prion disease in particular. The acquired knowledge will enable us to screen for compounds that could prevent further stages of the disease. Our goal is to transfer knowledge into pharmaceutical industry that is highly developed in Slovenia.   We are the only group in Slovenia working in the field of asymmetric catalysis. Aiming at the construction of new practical catalysts, their application would result in reduction of catalyst loadings still operating in a timely fashion, therefore improving the economics of industrial processes for the synthesis of enantiopure organic compounds. The interest of pharmaceutical industry for such robust catalytic processes to reliably supply the bulk active pharmaceutical ingredients (API) is increasing and we are actively collaborating with the local pharmaceutical companies, and developing collaborations with European academic groups. Also, we are introducing asymmetric catalysis to students of chemistry since it is only briefly presented to them during undergraduate studies.   Knowledge about the possible effectiveness of medicinal plants provides a starting point for the diversification of agricultural production in Slovenia in the field of cultivation of these plants. A strong interest in agriculture and related processing industries is reflected in search of new possibilities for the production and processing while achieving higher added value. At the same time, such programs create new green jobs and with the displacement of monocultures enrich natural landscape. Optimization of processes in brewing and their deeper understanding provide potential technological improvements and achieving higher competing demands in the brewing industry in Slovenia and on export markets.
Most important scientific results Annual report 2015, interim report
Most important socioeconomically and culturally relevant results Annual report 2015, interim report
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