Publications on the project |
078 Density functional study of the structure of guanine octets in aqueous medium |
Authors: | Ilchenko M.M., Dubey I.Ya. | |
Summary: | The structures and energies of guanine quartets and octets in water were determined by DFT (Density Functional Theory) calculations using M06-2X functional and 6-31G(d, p) basic set. Guanine quartets in vacuum were found to have not only the Hoogsteen or bifurcated, but also mixed system of hydrogen bonds; in water the latter two forms are transformed into the classic Hoogsteen-type structure. Four stable configurations of G-octets with D4, C4 and S4 symmetry formed by the pairs of guanine quartets with Hoogsteen, bifurcated or mixed system of H-bonds were identified. The most advantageous structure of the G-octet molecular system in aqueous medium was shown to be S4-symmetric structure consisting of the pair of mixed Hoogsteen-bifurcated type G-quartets. | |
Keywords: | DFT, G-octets, G-quartets, guanine, H-bonds | |
Edition: | Int. Rev. Biophys. Chem | | | 2011,
V. 2, N 3. – P. 82-86.,English |
078 Design and study of telomerase inhibitors based on G-quadruplex ligands |
Authors: | Negrutska V.V., Dubey L.V., Ilchenko M.M., Dubey I.Ya. | |
Summary: | We have summarized the results of our recent research on telomerase inhibitors and G-quadruplex DNA ligands. A series of potential enzyme inhibitors were synthesized and studied. These compounds were based on tricyclic heteroaromatic systems (thiazolobenzimidazoles phenazines, acridones), amino-substituted cyanines and natural and synthetic porphyrins and their metalocomplexes. A number of compounds, including cyanines and especially porphyrin derivatives and conjugates, were found to efficiently inhibit telomerase at low micromolar concentrations in the in vitro TRAP assay. Porphyrins demonstrated antiproliferative activity in tumor cell cultures at micro- and nanomolar concentrations. Spectral-fluorescent and electrophoretic experiments were performed to investigate the interaction of ligands with duplex and quadruplex DNA, and in many cases binding mode was established. Convenient G-octet model of G-quadruplex was developed to study the ligand-target binding using quantum-chemical methods. QM/MM hybrid approach ONIUM2 was employed to model the interaction of small molecules with Tel22 quadruplex DNA. | |
Keywords: | telomerase, G-quadruplex, TRAP, antitumor agents, porphyrins, molecular modeling | |
Edition: | Biopolym. Cell | | | 2013,
V. 29, N 3. – P. 169-176. ,English |
078 Self-assemblies of tricationic porphyrin on inorganic polyphosphate |
Authors: | Zozulya V., Ryazanova O., Voloshin I., Ilchenko M., Dubey I., Glamazda A., Karachevtsev V. | |
Summary: | Self-assemblies formed by the new synthesized tricationic porphyrin derivative (TMPyP3+) on the polyanionic inorganic polyphosphate (PPS) in aqueous solution were studied using different spectroscopic techniques and DFT calculation method. From the fluorescence quenching of the bound TMPyP3+ molecules and their Raman spectra we conclude that porphyrin chromophores form the stable - stacking-assemblies onto PPS polyanions. The transformation of the Soret band in absorption spectra at different PPS/TMPyP3+concentration ratios evidences that the assemblies are mixtures of J- and H-aggregates. Molecular modeling performed shows that the flexibility of PPS strand allows a realization of spiral or “face-to-face” one-dimensional structures formed by porphyrin molecules arranged in parallel and antiparallel mode. The peculiarity of PPS structure allows a formation of two porphyrin stacks on opposite sides of polymer strands that result in appearance of higher-order aggregates. Their size was estimated from the light scattering data. Distinctions between TMPyP3+ and TMPyP4 aggregation on PPS template are discussed. | |
Keywords: | cationic meso-porphyrin, porphyrin aggregation, polyphosphate, polarized fluorescence, light scattering, absorption | |
Edition: | Biophys. Chem. | | | 2014,
V. 185. – P. 39-46.,English |
078 Nanoconjugates of antitumor agents based on specific ligands of quadruplex DNA – telomerase inhibitors |
Authors: | Dubey L.V., Kostaina V.G., Negrutska V.V., Ilchenko M.M. Kuziv Ya.B., Dubey I.Ya. | |
Summary: | A series of new heterocyclic compounds of various classes were synthesized. Some of porphyrin and acridine derivatives were found to inhibit telomerase and show antiproliferative activity in vitro at low micromolar concentrations. Nanoconjugates of active enzyme inhibitors with biocompatible polymer supports (dextran, polymalic acid) were obtained and studied. The ability of synthesized nanomaterials to gradually release the attached bioactive compounds was demonstrated. In the future inhibitors and nanoconjugates could become drug candidates for the therapy of oncological diseases Thus, this work combined two main current approaches to novel anticancer agents: search of compounds aimed at highly specific biological targets and development of systems of their delivery to the tumor cell.. | |
Keywords: | quadruplex DNA, telomerase, antitumor agents, porphyrins, acridines, dextran, polymalic acid, nanoconjugates | |
Edition: | “Nanosized systems and nanomaterials: research in Ukraine” (ed. by A.G. Naumovets): NAS of Ukraine. – Kyiv, “Academperiodika” | | | 2014,
C. 503-509,Russian |
The events in the framework of the project |
078 078 078 078 078 078 078 078 078 078 078
|
078 5. Nanobiotechnology Purpose: Expected results:Release of new product: material Stage 1: Stage 2: Stage 3: Stage 4: Stage 5:
|