Strucure of Biosystems and Molecular Materials - Radek Marek

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.

list / cards

SELECTED PUBLICATIONS

2017

• BORA, P. L; NOVAK, M; NOVOTNY, J; FOROUTAN-NEJAD, C; MAREK, R, 2017:Supramolecular Covalence in Bifurcated Chalcogen Bonding. CHEMISTRY-A EUROPEAN JOURNAL
• FIALA, T; LUDVIKOVA, L; HEGER, D; SVEC, J; SLANINA, T; VETRAKOVA, L; BABIAK, M; NECAS, M; KULHANEK, P; KLAN, P; SINDELAR, V, 2017:Bambusuril as a One-Electron Donor for Photoinduced Electron Transfer to Methyl Viologen in Mixed Crystals. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 139 (7), p. 2597 - 2603.
• GAJARSKY, M; ZIVKOVIC, ML; STADLBAUER, P; PAGANO, B; FIALA, R; AMATO, J; TOMASKA, L; SPONER, J; PLAVEC, J; TRANTIREK, L, 2017:Structure of a Stable G-Hairpin. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 139 (10), p. 3591 - 3594.
• JANCARIKOVA, G; HOUSER, J; DOBES, P; DEMO, G; HYRSL, P; WIMMEROVA, M, 2017:Characterization of novel bangle lectin from Photorhabdus asymbiotica with dual sugar-binding specificity and its effect on host immunity. PLOS PATHOGENS 13 (8)
• KEJNOVSKA, I; BEDNAROVA, K; RENCIUK, D; DVORAKOVA, Z; SKOLAKOVA, P; TRANTIREK, L; FIALA, R; VORLICKOVA, M; SAGI, J, 2017:Clustered abasic lesions profoundly change the structure and stability of human telomeric G-quadruplexes. NUCLEIC ACIDS RESEARCH 45 (8), p. 4294 - 4305.
• NOVAK, M; MAREK, R; FOROUTAN-NEJAD, C, 2017:Anti-Electrostatic CH-Ion Bonding in Decorated Graphanes. CHEMISTRY-A EUROPEAN JOURNAL 23 (59), p. 14931 - 14936.
• NOVOTNY, J; VICHA, J; BORA, PL; REPISKY, M; STRAKA, M; KOMOROVSKY, S; MAREK, R, 2017:Linking the Character of the Metal-Ligand Bond to the Ligand NMR Shielding in Transition-Metal Complexes: NMR Contributions from Spin-Orbit Coupling. JOURNAL OF CHEMICAL THEORY AND COMPUTATION 13 (8), p. 3586 - 3601.
• YURENKO, Y. P; NOVOTNÝ, J; MAREK, R, 2017:Weak supramolecular interactions governing parallel and antiparallel DNA quadruplexes: Insights from large-scale QM analysis of experimentally-derived models. Chemistry - A European Journal
• YURENKO, YP; NOVOTNY, J; MAREK, R, 2017:Weak Supramolecular Interactions Governing Parallel and Antiparallel DNA Quadruplexes: Insights from Large-Scale Quantum Mechanics Analysis of Experimentally Derived Models. CHEMISTRY-A EUROPEAN JOURNAL 23 (23), p. 5573 - 5584.

2016

• BADRI, Z; FOROUTAN-NEJAD, C, 2016:Unification of ground-state aromaticity criteria - structure, electron delocalization, and energy - in light of the quantum chemical topology. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 18 (17), p. 11693 - 11699.
• BRANNA, P; CERNOCHOVA, J; ROUCHAL, M; KULHANEK, P; BABINSKY, M; MAREK, R; NECAS, M; KURITKA, I; VICHA, R, 2016:Cooperative Binding of Cucurbit[n]urils and beta-Cyclodextrin to Heteroditopic Imidazolium-Based Guests. JOURNAL OF ORGANIC CHEMISTRY 81 (20), p. 9595 - 9604.
• DUREC, M; ZACCARIA, F; GUERRA, CF; MAREK, R, 2016:Modified Guanines as Constituents of Smart Ligands for Nucleic Acid Quadruplexes. CHEMISTRY-A EUROPEAN JOURNAL 22 (31), p. 10912 - 10922.
• FOROUTAN-NEJAD, C; ANDRUSHCHENKO, V; STRAKA, M, 2016:Dipolar molecules inside C-70: an electric field-driven room-temperature single-molecule switch. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 18 (48), p. 32673 - 32677.
• MIKULASEK, K; JARON, KS; KULHANEK, P; BITTOVA, M; HAVLIS, J, 2016:Sequence-dependent separation of trinucleotides by ion-interaction reversed-phase liquid chromatography A structure-retention study assisted by soft-modelling and molecular dynamics. JOURNAL OF CHROMATOGRAPHY A 1469 , p. 88 - 95.
• NOVAK, M; FOROUTAN-NEJAD, C; MAREK, R, 2016:Modulating Electron Sharing in Ion-pi-Receptors via Substitution and External Electric Field: A Route toward Bond Strengthening. JOURNAL OF CHEMICAL THEORY AND COMPUTATION 12 (8), p. 3788 - 3795.
• NOVAK, M; FOROUTAN-NEJAD, C; MAREK, R, 2016:Solvent effects on ion-receptor interactions in the presence of an external electric field. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 18 (44), p. 30754 - 30760.
• NOVOTNY, J; BAZZI, S; MAREK, R; KOZELKA, J, 2016:Lone-pair-pi interactions: analysis of the physical origin and biological implications. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 18 (28), p. 19472 - 19481.
• NOVOTNY, J; SOJKA, M; KOMOROVSKY, S; NECAS, M; MAREK, R, 2016:Interpreting the Paramagnetic NMR Spectra of Potential Ru(III) Metallodrugs: Synergy between Experiment and Relativistic DFT Calculations. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 138 (27), p. 8432 - 8445.
• PHULWALE, BV; MISHRA, SK; NECAS, M; MAZAL, C, 2016:Phenanthrylene-butadiynylene and Phenanthrylene-thienylene Macrocycles: Synthesis, Structure, and Properties. JOURNAL OF ORGANIC CHEMISTRY 81 (15), p. 6244 - 6252.
• TRISKOVA, I; FIALA, R; TRNKOVA, L, 2016:Redox Processes of Guanine Moieties in DNA Heptamers Related to Hydrogen Evolution. ELECTROANALYSIS 28 (11), p. 2841 - 2848.
• VAVRINSKA, A; ZELINKA, J; SEBERA, J; SYCHROVSKY, V; FIALA, R; BOELENS, R; SKLENAR, V; TRANTIREK, L, 2016:Impact of nucleic acid self-alignment in a strong magnetic field on the interpretation of indirect spin-spin interactions (vol 64, pg 53, 2016). JOURNAL OF BIOMOLECULAR NMR 65 (1), p. 49 - 49.
• VAVRINSKA, A; ZELINKA, J; SEBERA, J; SYCHROVSKY, V; FIALA, R; BOELENS, R; SKLENAR, V; TRANTIREK, L, 2016:Impact of nucleic acid self-alignment in a strong magnetic field on the interpretation of indirect spin-spin interactions. JOURNAL OF BIOMOLECULAR NMR 64 (1), p. 53 - 62.
• VICHA, J; MAREK, R; STRAKA, M, 2016:High-Frequency C-13 and Si-29 NMR Chemical Shifts in Diamagnetic Low-Valence Compounds of TII and Pb-II: Decisive Role of Relativistic Effects. INORGANIC CHEMISTRY 55 (4), p. 1770 - 1781.
• VICHA, J; MAREK, R; STRAKA, M, 2016:High-Frequency H-1 NMR Chemical Shifts of Sn-II and Pb-II Hydrides Induced by Relativistic Effects: Quest for Pb-II Hydrides. INORGANIC CHEMISTRY 55 (20), p. 10302 - 10309.
• YURENKO, YP; NOVOTNY, J; NIKOLAIENKO, TY; MAREK, R, 2016:Nucleotides containing variously modified sugars: energetics, structure, and mechanical properties. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 18 (3), p. 1615 - 1628.

2014

• BADRI, Z; BOUZKOVA, K; FOROUTAN-NEJAD, C; MAREK, R, 2014:Origin of the Thermodynamic Stability of the Polymorph IV of Crystalline Barbituric Acid: Evidence from Solid-State NMR and Electron Density Analyses. CRYSTAL GROWTH & DESIGN 14 (6), p. 2763 - 2772.
• FOROUTAN-NEJAD, C; MAREK, R, 2014:Potential energy surface and binding energy in the presence of an external electric field: modulation of anion-pi interactions for graphene-based receptors. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 16 (6), p. 2508 - 2514.
• FOROUTAN-NEJAD, C; SHAHBAZIAN, S; MAREK, R, 2014:Toward a Consistent Interpretation of the QTAIM: Tortuous Link between Chemical Bonds, Interactions, and Bond/Line Paths. CHEMISTRY-A EUROPEAN JOURNAL 20 (32), p. 10140 - 10152.
• FOROUTAN-NEJAD, C; VICHA, J; MAREK, R, 2014:Design of Stereoelectronically Promoted Super Lewis Acids and Unprecedented Chemistry of Their Complexes. CHEMISTRY-A EUROPEAN JOURNAL 20 (36), p. 11584 - 11590.
• HAVEL, V; SINDELAR, V; NECAS, M; KAIFER, AE, 2014:Water-mediated inclusion of benzoates and tosylates inside the bambusuril macrocycle. CHEMICAL COMMUNICATIONS 50 (11), p. 1372 - 1374.
• CHYBA, J; MORAVEC, Z; NECAS, M; MATHUR, S; PINKAS, J, 2014:Construction of Larger Molecular Aluminophosphate Cages from the Cyclic Four-Ring Building Unit. INORGANIC CHEMISTRY 53 (7), p. 3753 - 3762.
• NOVOTNY, J; YURENKO, YP; KULHANEK, P; MAREK, R, 2014:Tailoring the properties of quadruplex nucleobases for biological and nanomaterial applications. PHYSICAL CHEMISTRY CHEMICAL PHYSICS 16 (29), p. 15241 - 15248.
• VICHA, J; STRAKA, M; MUNZAROVA, ML; MAREK, R, 2014:Mechanism of Spin-Orbit Effects on the Ligand NMR Chemical Shift in Transition-Metal Complexes: Linking NMR to EPR. JOURNAL OF CHEMICAL THEORY AND COMPUTATION 10 (4), p. 1489 - 1499.
• YURENKO, YP; NOVOTNY, J; MITORAJ, MP; SKLENAR, V; MICHALAK, A; MAREK, R, 2014:Nucleic Acid Quadruplexes Based on 8-Halo-9-deazaxanthines: Energetics and Noncovalent Interactions in Quadruplex Stems. JOURNAL OF CHEMICAL THEORY AND COMPUTATION 10 (12), p. 5353 - 5365.

2013

• BADRI, Z; FOROUTAN-NEJAD, C; RASHIDI-RANJBAR, P, 2013:A theoretical survey on the D-7d [84]fullerene, a fullerene with two heptagon rings. COMPUTATIONAL AND THEORETICAL CHEMISTRY 1009 , p. 103 - 107.
• BADRI, Z; PATHAK, S; FLIEGL, H; RASHIDI-RANJBAR, P; BAST, R; MAREK, R; FOROUTAN-NEJAD, C; RUUD, K, 2013:All-Metal Aromaticity: Revisiting the Ring Current Model among Transition Metal Clusters. JOURNAL OF CHEMICAL THEORY AND COMPUTATION 9 (11), p. 4789 - 4796.
• BOUZKOVA, K; BABINSKY, M; NOVOSADOVA, L; MAREK, R, 2013:Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and C-13 NMR Chemical Shift Tensors. JOURNAL OF CHEMICAL THEORY AND COMPUTATION 9 (6), p. 2629 - 2638.
• DEBNATH, M; DUTTA, A; BISWAS, S; DAS, KK; LEE, HM; VICHA, J; MAREK, R; MAREK, J; ALI, M, 2013:Catalytic oxidation of aromatic hydrocarbons by mono-oxido-alkoxidovanadium(V) complexes of ONNO donor ethylenediamine-bis(phenolate) ligands. POLYHEDRON 63 , p. 189 - 198.
• PEKARIK, V; GUMULEC, J; MASARIK, M; KIZEK, R; ADAM, V, 2013:Prostate Cancer, miRNAs, Metallothioneins and Resistance to Cytostatic Drugs. CURRENT MEDICINAL CHEMISTRY 20 (4), p. 534 - 544.
• SPICHAL, Z; JANCARIK, A; MAZAL, C; PINKAS, J; PEKARKOVA, P; NECAS, M, 2013:Lanthanide coordination polymers with bis(diphenylphosphoryl)bicyclo[1.1.1]pentane. POLYHEDRON 62 , p. 83 - 88.
• STANDARA, S; KULHANEK, P; MAREK, R; STRAKA, M, 2013:Xe-129 NMR chemical shift in Xe@C-60 calculated at experimental conditions: Essential role of the relativity, dynamics, and explicit solvent. JOURNAL OF COMPUTATIONAL CHEMISTRY 34 (22), p. 1890 - 1898.

2012

• PEVEC, A; DEMSAR, A; PINKAS, J; NECAS, M, 2012:Synthesis of Organotitanium(IV) Fluoride Phosphates and the Crystal Structure of [(C5Me4Et)TiF(mu-F){mu-O2P(OSiMe3)(2)}](2). ACTA CHIMICA SLOVENICA 59 (1), p. 203 - 206.
• POURAYOUBI, M; NECAS, M; NEGARI, M, 2012:The double H-atom acceptability of the P=O group in new XP(O)(NHCH2C6H4-2-Cl)(2) phosphoramidates [X = C6H5O- and CF3C(O)NH-]: a database analysis of compounds having a P(O)(NHR) group. ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS 68 , p. O51 - O56.
• VICHA, J; DEMO, G; MAREK, R, 2012:Platinum-Modified Adenines: Unprecedented Protonation Behavior Revealed by NMR Spectroscopy and Relativistic Density-Functional Theory Calculations. INORGANIC CHEMISTRY 51 (3), p. 1371 - 1379.

1. Designing modified DNA fragments

Supervisor: prof. RNDr. Radek Marek, Ph.D.

Keywords: modified DNA quadruplexes, NMR spectroscopy, structure and biophysical properties

Literature:

• BAZZI, S.;NOVOTNÝ, J.;YURENKO, Y.;MAREK, R. Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands. Chemistry - A European Journal, Weinheim: Wiley-VCH, 2015, roč. 21, č. 26, s. 9414-9425. ISSN 0947-6539. doi:10.1002/chem.201500743.
   
• YURENKO, Y.;NOVOTNÝ, J.;SKLENÁŘ, V.;MAREK, R. Exploring non-covalent interactions in guanine- and xanthine-based model DNA quadruplex structures: A comprehensive quantum chemical approach. Physical Chemistry Chemical Physics, Cambridge: Royal Society of Chemistry, 2014, roč. 16, č. 5, s. 2072-2084. ISSN 1463-9076. doi:10.1039/C3CP53875C.
   
• YURENKO, Y.;NOVOTNÝ, J.;MITORAJ, M.P.;SKLENÁŘ, V.;MICHALAK, A.;MAREK, R. Nucleic acid quadruplexes based on 8-halo-9-deazaxanthines: Energetics and non-covalent interactions in quadruplex stems. Journal of Chemical Theory and Computation, Washington D.C.: American Chemical Society, 2014, roč. 10, č. 12, s. 5353-5365. ISSN 1549-9618. doi:10.1021/ct5007554.
   
• YURENKO, Y.;NOVOTNÝ, J.;NIKOLAIENKO, T.;MAREK, R. Nucleotides containing variously modified sugars: energetics, structure, and mechanical properties. Physical Chemistry Chemical Physics, Royal Society of Chemistry, 2016, roč. 18, č. 3, s. 1615-1628. ISSN 1463-9076. doi:10.1039/C5CP05478H.
   
• YURENKO, Y.;NOVOTNÝ, J.;SKLENÁŘ, V.;MAREK, R. Substituting CF2 for O4' in Components of Nucleic Acids: Towards Systems with Reduced Propensity to Form Abasic Lesions. Chemistry - A European Journal, Wiley, 2015, roč. 21, č. 49, s. 17933-17943. ISSN 0947-6539. doi:10.1002/chem.201502977.
   
• NOVOTNÝ, J.;YURENKO, Y.;KULHÁNEK, P.;MAREK, R. Tailoring the Properties of Quadruplex Nucleobases for Biological and Nanomaterial Applications. Physical Chemistry Chemical Physics, Cambridge: Royal Society of Chemistry, 2014, roč. 16, č. 29, s. 15241-15248. ISSN 1463-9076. doi:10.1039/C4CP00541D.