Project acronym SLONMR Project title Use of NMR

Project acronym: SLONMR Project title: Use of NMR Spectroscopy in Combination with Computational Methods on Systems of Biological Interest Slovenian NMR Centre @ NIC (www. nmr. ki. si) Basic info: NMR centre offers the necessary infrastructure and service for collection and processing of NMR spectra to all institutions and companies that use NMR in their research and development as part of basic or application research projects. 600 MHz NMR spectrometer is used in the studies of threedimensional structure and dynamics of complex systems with the high molecular mass such as proteins and nucleic acids. The two 300 MHz instruments are used by synthetic organic chemists, for solid-state measurements and wine analyses as well as for routine analyses in pharmaceutical, chemical, food and other industries. Research: • NMR centre cooperates with many groups and laboratories on over 46 basic and applied projects in year 2001 (list available at http: //www. nmr. ki. si/research) • 57 publications in international journals in 2000 1

2 NATIONAL INSTITUTE OF CHEMISTRY Laboratories NMR center

NATIONAL INSTITUTE OF CHEMISTRY RESEARCH AREAS STRUCTURAL, THEORETICAL CHEMISTRY ANALYTICAL CHEMISTRY AND ECOLOGY CHEMICAL ENGINEERING ORGANIC AND INORGANIC MATERIALS BIOTECHNOLOGY 3

NIC FUNDING INSTITUTE STAFF Number of the Employees: 185 PUBLISHED WORK (papers, books, chapters, patents) 4

5 High Resolution Nuclear Magnetic Resonance Spectroscopy ? ? ?

Slovenian NMR center 6

Slovenian NMR center 7

Slovenian NMR center 8

Slovenian NMR center 9 Research activities (http: //www. nmr. ki. si/research): Current research projects at NMR centre involve: • Interactions of metal ions with nucleic acids and the development of new NMR techniques for the localization of cation binding of a variety of non-B-form DNA secondary structures, including those which contain G-quartets • Structure and dynamics of proteins, • Structural characterization of protein/peptide - ligand interactions, • Interaction of antibiotics with the cell membrane of bacteria, • Determination of very low concentrations of various residues in drugs, • Structure and purity of polymer materials, as well as characterization of side products in polymerisation reactions, • Structure and interactions in solid state materials such as zeolites, • Screening of the binding affinities to a target protein via SAR by NMR approach using either synthetic combinatorial libraries or libraries from the plant materials, • Development of methods of molecular modelling relevant for computational support of NMR spectroscopy. An important task of NMR centre is its role in education, offering help at collection and interpretation of NMR data to students from B. Sc. to Ph. D. level. Equipment: Varian NMR spectrometers: 600 MHz Unity Inova, 300 MHz Unity plus, 300 MHz Unity Inova with the broad selection of probes, workstations Sun Ultra 60 and Sun Ultra 1 -140.

Slovenian NMR center 10 Objectives: Proposal promotes collaboration of our NMR centre with groups around Europe by facilitating exchange visits of graduate students and post-docs as well as senior scientists which were limited up till now due to the absence of appropriate funding. We have close contacts with colleagues in several fellow NMR facilities around Europe (Uppsala-Sweden, Poznan-Poland, Graz-Austria, Munich-Germany, Leuven-Belgium, Montpellier-France, Sheffield-UK, Athens-Greece, Budapest-Hungary). Our research objectives cover the following broad areas where NMR spectroscopy can be used as a method of choice: 1. Characterization of conformationaly restricted nucleosides (WP 1), 2. Development of new methodology to study metabolism of carbohydrates with deuterium NMR spectroscopy (WP 2), 3. Complex enzymatic reactions (WP 3), 4. Nucleic acid structure and conformation (WP 4), 5. Characterization of metastable states and conformational transitions of proteins involved in disease (WP 6), 6. Theoretical and experimental studies of intramolecular hydrogen bonding (WP 8), 7. Conformational analysis of peptidomimetic drugs (WP 9), 8. Interactions of glycopeptide antibiotics by membrane bilayers (WP 10), 9. Structural characterization of natural products like terpenoids and flavonoids (WP 11).

Slovenian NMR center 11 Experiences & Comments: • Centre of Excellence plays a very positive role in promoting collaborations of our NMR centre with groups around Europe. • Status of EU Centre of Excellence has strengthened the position of NMR centre in Slovenia. • Frustrations in contacts with huge bureaucratic apparatus. • Delays in response from administration. • Very difficult to get clear answer on a specific question during preparation (problems with even two types of proposal forms) and realisation phases (e. g. how to prepare cost statements). • Greater mobility is a nice idea, but will probably take some more time to make it a reality. • Hopes for future investment from EC in research equipment of Slovenian NMR center. New higher field NMR spectrometer would serve a role of regional infrastructure and facility in Central and East Europe. • Overall experience is very positive and clearly stimulating.