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Acta Cryst. (2014). A70, C968
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Nucleobases belong to purine and pyrimidine family and constitute a biologically crucial group of compounds thank to their relation to nucleic acids. Specific interactions between these moieties are responsible for maintaining a proper structure of DNA, namely: hydrogen bonding and π-π stacking interactions (between aromatic ring fragments). Furthermore, many modifications of natural nucleobases serve as drugs, but some could be extremely harmful. In view of the above, investigating the properties of analogues of nucleobases may contribute to our knowledge about nucleic acid properties in general and give an opportunity to find novel ligands binding to DNA, what is essential for drug design. Within this project two modified nucleobases were examined: 2,6-diaminopurine (DAP) and isocytosine (iC). DAP is a derivative of the adenine and iC is an isomer of cytosine. These compounds do not appear naturally in nucleic acids, however, can be used to compare Watson-Crick pairing in DNA and pairing of alternative bases. High resolution X-ray diffraction experiments were carried out to obtain appropriate data for charge density analysis. A comprehensive study of crystal packing and energetic features of the analysed systems was conducted. The nature of intermolecular interactions, structural motifs and crystal packing was analysed via Hirshfeld surface analysis [1], charge density distribution examination, QTAIM (Quantum Theory of Atoms in Molecules) [2] and theoretical calculations (gas phase dimers and periodic). Implications of the observed interactions for biological systems are discussed. This study was supported by the Polish Ministry of Science and Higher Education within the Diamond Grant No DI 2011012441.

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Acta Cryst. (2014). A70, C970
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Electron density is a key factor in determining properties of molecules. Knowledge of the electron density distribution allows to determine not only the 3D structure of molecules, but also various one-electron properties (electric moments, electrostatic potential, electrostatic interaction energy, etc.). X-ray diffraction is a great tool for obtaining this kind of information. For macromolecules, however, quantitative determination of charge density from experiment is possible on rare occasions only. We will present that with the University at Buffalo pseudoatom database (UBDB) approach [1,2] it is now possible to reconstruct electron density of any macromolecular system for which atomic coordinates are available. The approach is fast and opens an excellent opportunity to investigate macromolecular complexes by means of topological analysis of electron density (and derivatives thereof), electrostatic interaction energy analysis, and many others. The results of our studies on sunitinib (SU) will illustrate the possibilities of the approach. SU is an inhibitor of tyrosine kinases and was approved as a drug in 2006. Comprehensive analysis of the SU malate crystal and SU complexes with a series of protein kinases was carried out. The high resolution single crystal X-ray measurement and UBDB approach served as the basis for the reconstruction of the charge density of SU and the protein complexes. Hirshfeld surface and topological analyses revealed a similar interaction pattern in the SU malate crystal to that in the protein binding pockets. SU forms nine preserved bond paths corresponding to hydrogen bonds and also to the C-H...O and C-H...π contacts common for all analyzed kinases. It interacts typically with similar electrostatic interaction energy with the studied proteins and can adjust its conformation to fit the binding pocket in a way to enhance the electrostatic interactions. Such behavior can be responsible for a broad spectrum of action of SU as kinase inhibitor.
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