Research areas
- Structure and biophysical properties of natural compounds
- Structural Chemistry of Biosystems
- Computational desing of receptors and nanodevices
Main objectives
- Design and properties of modified DNA quadruplexes
- Development of metallodrug-carrier systems for delivery and targeting: novel prodrugs based on diamagnetic Pt(IV) and paramagnetic Ru(III) complexes
- Understanding the role of various non-covalent interactions in supramolecular assemblies - NMR spectroscopy and computational analysis
Content of research
Design and properties of modified DNA quadruplexes and quadruplex-binding ligands.Very recently, we have obtained quite interesting results by in silico design of artificial bases for quadruplex nucleic acids. We are implementing several new structural modifications in the base and sugar regions. Designed systems are further evaluated by methods of molecular dynamics and PMF approaches and the most promising candidates are suggested to our collaborators for preparation of monomeric units suitable for subsequent oligonucleotide solid-phase synthesis. Theoretically predicted properties of the modified systems are investigated experimentally by using NMR spectroscopy.
Smart metallodrug-carrier systems for delivery and targeting.The knowledge of in silico design is used to develop new metallodrugs with optimized binding to macrocyclic cavitands employed as drug carriers. These macrocyclic carriers improve a delivery of the metallodrug to the target in cancer cell and reduce many side effects during the drug transport. Designed systems are synthesized, characterized by NMR spectroscopy (including paramagnetic NMR for ruthenium complexes), and interpreted using correlations with theoretical NMR calculations. The NMR spectroscopy is used for determining the drug-carrier binding constants and conditions for the efficient drug release. Potential drug candidates are suggested for biological testing.
Receptors and nanodevices.Computational design of receptors and nanodevices derived from graphene sheets and fullerenes in external electric and magnetic fields is based on our know-how and well-established methodology (e.g., see our papers PCCP 2014, Chem. Eur. J. 2014). In addition, novel catalysts based on the transition-metal complexes are designed and investigated. The high-level theoretical methods are used to predict the binding and electromagnetic properties of these systems
3D structure of the DNA quadruplex with fluorinated deazaxanthine bases.
