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2010 Vol VIIІ #2

Do CH...O hydrogen bonds really stabilize DNA base pairs? Results of quantum chemical analysis

Ye.P. Yurenko

Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotnogo Str., Kyiv, 03680, Ukraine

Summary. We have performed a comprehensive geometrical, vibrational and electron topological analysis of hydrogen bonds in DNA base pairs involving canonical and rare tautomers. Quantum chemical calculations at the MP2/6-31G(d,p) and DFT B3LYP/6-31G(d,p) levels of theory allowed to establish that CH...O contacts are real hydrogen bonds, whose strengths are close to 1 kcal/mol, i.e. exceed kT value at the room temperature.

Keywords: hydrogen bonds, tautomers, DNA base pairs, topological analysis of electron density.

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The relationship among biological membranes and signaling mediators. I. How can this be explained?

B.A. Kurchii

Institute of Plant Physiology and Genetics
31/17 Vasylkivska Str., 03022, Kyiv, Ukraine

Summary. In this paper I briefly reviewed the relevance of a membrane structure to biological signal systems in the light of current knowledge. Also this paper deals with some of the features of biological membranes that are related to functions that they perform in the living cells. I describe how are conjoined between themselves fatty acids in the membrane layer. The discussed data have been chosen with the advances of our understanding of the membrane molecular organization and their role in the perception of signals, transformation and transduction them to targets and response pathways. One of the outstanding conundrums concerning the perception mechanism is how this process deals with genomic and non-genomic responses.

Keywords:
lipids, membranes, oxidants, receptors, signaling.

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The relationships among biological membranes and signaling mediators. II. How do the receptors find and identify their targets?

B.A. Kurchii

Institute of Plant Physiology and Genetics
31/17 Vasylkivska Str., 03022, Kyiv, Ukraine

Summary. Although many components of the signaling pathways are known, nevertheless, how mitogen-activated protein kinase signaling pathways relay, integrate and transmit signals from a diverse range of intracellular and extracellular stimuli to nuclear DNA remains an open question for now. How do RNA polymerase or DNA polymerases find and identify their targets avoiding fruitless searching through megabases of non-target DNA? In this paper I review how this sequence searching may be done. I described an alternative perception mechanism of intracellular and extracellular stimuli and transduction them to nuclear DNA using as a messenger (a receptor) the short DNA strands i.e. primers. I believe that so-called receptors (transcription factors) are synthesized simultaneously with membranes and stored in the rafts of membranes upon their damage by chemical or physical factors. Liberated during membrane destruction these receptors (signaling molecules), called by us as gene keys, conjoin with the template DNA strands at the promoter (gene locks) through non-covalent bonds with A-T base pairs. Thus, the gene key dictates when, where and what specific genes are transcribed.

Keywords: DNA, membranes, primers, receptors, signaling.

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The 2-deoxy-D-ribopyranose molecule exhaustive quantum-mechanical conformational analysis

Т.Yu. Nikolaienko1, L.А. Bulavin1, D.M. Hovorun2,3

1 National Taras Shevchenko University of Kyiv
2 Hlushkova Ave., build. 1, Kyiv, 03022, Ukraine

2 Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotny Str., Kyiv, 03680, Ukraine

3 Institute of High Technologies of Taras Shevchenko Kyiv National University
2 Hlushkova Ave., build. 1, Kyiv, 03127, Ukraine

Summary. The conformational analysis of the biologically important 2-deoxy-D-ribose molecule adopting the form of pyranose ring in α- and β-anomeric states has been carried out by the quantum-mechanical density functional theory method at the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) theory level. As many as 74 conformations of its α- and 83 conformations of β-anomeres were detected with relative gas-phase Gibbs free energies under standard conditions within 0÷16,8 and 0÷14,7 kcal/mole respectively. The thermodynamically equilibrium populations of different forms of the 2-deoxy-D-ribose molecule in gas phase at T=298,15 K have been shown to be: 53 % (α-pyranose) : 23 % (β-pyranose): 22 % (α-furanose) : 2 % (β-furanose). In 6 conformations of 2-deoxy-b-D-ribopyranose the O1'βH···HC4' intramolecular HH-contact having the energy of 1,4÷1,9 kcal/mole was revealed.

Keywords: 2-deoxy-D-ribose, conformational analysis, (di)hydrogen bonds.

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Intramolecular hydrogen bonds in conformers of low molecular models of 2’-deoxyribopolinucleotides sugar-phosphate frame: electron density topology analysis

I.S. Voiteshenko1, R.O. Zhurakivsky2, L.A. Bulavin1, D.M. Hovorun2,3

1 National Taras Shevchenko University of Kyiv
2 Hlushkova Ave., build. 1, Kyiv, 03022, Ukraine

2 Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotny Str., Kyiv, 03680, Ukraine

3 Institute of High Technologies of Taras Shevchenko Kyiv National University
2 Hlushkova Ave., build. 1, Kyiv, 03127, Ukraine

Summary. The set of intramolecular hydrogen (Н) bonds, that stabilize found conformers of low molecular model compounds the 2’-deoxyribopolinucleotides bisugar-phosphate frame, was described by method of electron density topology analysis at DFT B3LYP/6-31++G(d,p) and DFT B3LYP/6-31G(d,p) theory levels. Their electron-topological, energy and conformative properties are presented. Intramolecular C2’n-1H2...O4’n H-bond between adjacent sugar residues was firstly observed, it presence is common structure factor supporting conformers similar to native DNA B-form.

Keywords: model sugar-phosphate residue, intramolecular hydrogen and dihydrogen bonds, quantum chemical investigations, electron density topology analysis.

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Synthesis and biological activity of Ѕ-geterilsubstitutes of L-cysteine and its analogs

Y.Y. Petrusha, L.A. Omelyanchik, A.A. Brazhko, M.P. Zavgorodny

Zaporizhzhya National University
66 Zhukovskogo Str., Zaporizhzhya, 69600, Ukraine

Summary. It was synthesized new Ѕ-geterilsubstitutes of L-cysteine and its structural analogs, it was investigated their acute toxicity and antiradical activity on model autooxidation of adrenaline.

Keywords: Ѕ-geterilsubstitutes of L-cysteine, acute toxicity, antiradical activity.

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Study of immunocorrecting properties of 4-phosphorilated derivatives of 1,3-oxazole and 1,3-thiazole under short- and long-term suppressive effects of cyclophosphane

L.O. Metelitsa, I.M. Kopernik, K.M. Kondratyuk, O.V. Golovchenko,
S.V. Popil’nichenko, V.V. Prokopenko, V.S. Brovarets


Institute of Bioorganic Chemistry and Petrochemistry NAS Ukraine
1 Murmanska Str., Kyiv, 02660, Ukraine

Summary. Ability of 4-phosphorylated derivatives of 1,3-oxazole and 1,3-thiazole to correct of short-term (1-2 days) and long duration (7 days) immunosuppression caused by cyclophosphan have been studied. The highest positive recuperative effect was discovered for dimethyl ester of 5-chloro[2-(4-chlorophenyl)-1,3-thiazol4-yl]thiophosphonic acid. Introduction of this compound to immunocompromized mice allows full restoring of thymus state suppression formed by cyclophosphan during 1 day and depression of spleen state caused by suppressor during up to 7 days.

Keywords: phosphorylated derivatives of 1,3-oxazole and 1,3-thiazole, thymus, spleen, immunosuppression, cyclophosphane.

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Quinazoline inhibitors of protein kinase FGFR1

A.A. Gryshchenko1, V.G. Bdzhola1, S.S. Lukashov1, L.V. Pletnyova1,
R.V. Chepurna
1, I.V. Zhitnetsky2, S.M. Yarmoluk1

1 Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotnogo Str., Kyiv, 03680, Ukraine

2 National University of Food Technologies
68 Volodymirs’ka Str., Kyiv, 01601, Ukraine

Summary. Protein kinase FGFR1 plays a key role in oncogenic transformation and oncovasculogenesis. Inhibitors of this kinase can be used as anticancer drugs. Protein kinase FGFR1 inhibitors searching were performed among quinazoline derivatives. 40 compounds from 1256 quinazolone derivatives have been chosen using virtual screening. The most active compound was 4-chloro-2-(6,7-dimetoxy-quinazolin-4-ylamino)-phenol (ІС50 0.1 μМ). Structure—activity relationship of tested compounds was investigated and binding mode for this compounds class in FGFR1 ATP-site was proposed.

Keywords: protein kinase FGFR1, quinazoline, docking.

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Synthesis of 3-(quinoline-2-on-3-yl)propanoic acids

А.R. Synyugin, M.O. Chekanov, S.S. Lukashov, S.M. Yarmoluk

Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Zabolotnogo Str., Kyiv, 03680, Ukraine

Summary. For the first time, it has been synthesed by two alternative ways and described series of 3-(quinoline-2-on-3-yl)propanoic acids.

Keywords: 2-quinolones, 2-chloroquinolines, 3-(quinoline-2-on-3-yl)propanoic acids.

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Synthesis and in vitro antibacterial activity of 3-(5-amino-6(2,3-dichlorophenyl)-1,2,4-triazin-3-yl)-2-aryl-quinazoline-4(3H)-ones

G. Nagarajan1, S. Kavimani2

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, PRIST University Thanjavur
Tamilnadu, India-614904

2 Department of Pharmacology, College of Pharmacy, Mother Teresa Institute
of Pharmaceutical sciences and research
Puducherry, Tamilnadu, India-605006

Summary. In the present study some new 3-(5-amino-6(2,3-dichlorophenyl)-1,2,4-triazin-3-yl)-2-aryl-quinazoline-4(3H)-ones (3a-3f) was synthesized. The newly synthesized compounds were characterized on the basis of elemental analysis, IR and 1H-NMR spectra. All the synthesized compounds were tested for their antibacterial activity against 20 strains of Gram positive and Gram negative bacteria. Among the compounds tested, the compounds 3a & 3f showed good antimicrobial activity in comparison to standard sulphamethoxazole. Compound 3f was found to be most active in the series against H.pylori with MIC 25 µg/mL.

Keywords: quinazolinones, in vitro antibacterial activity, MIC value.

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Peculiarities of synthesis and 1H NMR spectroscopy of Zirconium and Hafnium phthalocyanine complexes

V.Ya. Chernii

Vernadskii Institute of General and Inorganic Chemistry, NAS of Ukraine
Ukraine, Kyiv, Palladin Ave., 32/34

Summary. With the use of 1H NMR spectroscopy it was shown that synthesis of phthalocyanine complexes by fusing of o-phthalodinitrile and zirconium or hafnium tetrachlorides leads to the formation of series of side chlorinated metallophthalocyanines. Addition of 2-methylnaphtalene to the reaction mixture prevents the macrocycle chlorination and allows obtaining of zirconium and hafnium phthalocyanine of high purity.

Keywords: 1H NMR spectroscopy, zirconium and hafnium phthalocyanine complexes.

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