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Projects / Programmes source: ARIS

Nmr studies of nucleic acids structure and their interactions with metal ions

Research activity

Code Science Field Subfield
1.05.00  Natural sciences and mathematics  Biochemistry and molecular biology   

Code Science Field
P320  Natural sciences and mathematics  Nucleic acids, protein synthesis 
Keywords
nucleic acids, NMR spectroscopy, metal ion interactions, G-quartet, conformational analysis
Evaluation (rules)
source: COBISS
Researchers (4)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  19789  PhD Martin Črnugelj  Chemistry  Researcher  2002 - 2004  39 
2.  10082  PhD Janez Plavec  Chemistry  Head  2002 - 2004  1,255 
3.  21425  PhD Miha Plevnik  Pharmacy  Researcher  2002 - 2004  39 
4.  17918  PhD Matjaž Polak  Biochemistry and molecular biology  Researcher  2002 - 2004  56 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  20,996 
Abstract
In the project we propose to study interactions of metal ions with nucleic acids. 3D structure of DNA and RNA and subsequently their role and function are defined by metal ions. The presence of metal ions is required in many if not all biochemical processes in the cell. Formation of multistranded nucleic acid structures like Guanine-quartets requires the presence of cations. Our primary tool will be NMR spectroscopy. We propose to study the sequence-specific binding of 15N isotopically labeled ammonium binding probes by multinuclear NMR spectroscopy. Our model will be DNA oligonucleotides with sequence of guanine building blocks which are expected to form G-quadruplex structures. G-quartet structures are especially interesting from the point of cation binding, because they form a very stable structure, which can tolerate a wide variation in the details of backbone structure, including strand orientations, glycosidic conformations, and connecting loops length. Additionally, G-quartets represent an ideal framework for assembling many different structures including aptamers of very different specificities which can bind a desired molecular target. Our results will help to explain what governs the binding of cations to the nucleic acids and how much the interaction depends upon probe size and its charge density. The development of structural probes for cation localization that bind to DNA in solution will provide necessary structural information and additionally assist in the design of new cation probes. Deeper understanding of the functional role of G-quartets in biological proceses like their role in telomeric ends of DNA in cell, in aging and cancer diseases will be of assistance in the development of anticancer and antitumor drugs.
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