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2004 Vol I #1-2

 

The three-dimensional architecture of eukaryotic chromatin: zigzag-shaped band of DNA is disposed between two layers of nucleosomes forming a chromosome

B. A. Kurchii

IInstitute of Plant Physiology and Genetics
131/17 Vasylkivska Str., Kyiv, 03022, Ukraine 

Abstract: Three-layered structure of individual eukaryotic nucleosomes and the DNA packaging in the form of zigzag-shaped band are proposed. Nucleosome histones are grouped into three layers: L1 (H3-H4), L2 (H2A-H2B), and L3 (H1 or H5). Each layer realizes different functions. The L1 layer is conjugated with DNA ribbon by hydrogen bonds between amino acids of nucleosomes and a phosphate group of DNA. The L2 layer glues all nucleosomes forming the nucleosomal layer of the chromosome. The L3 layer is functioning as a protective shell for L1 and L2 histone layers. The eukaryotic chromosome is proposed to compose of two nucleosome layers, the DNA being disposed between them in a «zigzag folding» band. Three nucleosomes are arranged into a row along the long axis of the chromosome and form a nucleosomal triplet, a basic structural subunit of the chromosome. Parental nucleosomes do not undergo disruption processes during replication and transcription

Key words: chromatin, histones, nucleosome, nucleosomal triplet, snaky model of DNA packaging, «zigzag folding» ribbon of DNA.

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3,5-Diarylidenebicyclopentano[b,e]pyridines — a new class of fluorescent dyes. 2. Synthesis and determination of conformation in the solutions. Tri-azacrown- and hexa-(aminomethyl)-substituted derivatives

V. F. Valyuk, O. V. Grygorovych1, A. O. Doroshenko1,
V. G. Pivovarenko

Chemistry Faculty, Taras Shevchenko National University of Kyiv
64 Volodymyrska Str., Kyiv, 01033, Ukraine
1Institute of Chemistry V. N. Karazin National University (Kharkiv), 4 Svoboda sqr., Kharkiv, 61077, Ukraine

Abstract: To study the fluorescent properties and to develop new types of ion and pH sensors, several series of 3,5-diarylmethylene-8-arylbicyclopentano[b,e]pyridines were synthesized. Molecular geometry of the synthesized dyes in solutions was studied by 1H-NMR, electron absorption and fluorescence spectrometry. The spectral data testify all the compounds exist in E-configuration of their styryl residues. The most planar molecular conformation is typical for the compounds with five-membered side aromatic moieties. The dependence of fluorescence quantum yield and emission band position upon the structure and conformation of the molecule of compounds studied in the solution, as well as on the nature of the solvent were estimated and explained. We estimated the fluorescence quantum yield of substances obtained and explained its dependence upon the structure and conformation of their molecules in solution as well as upon the solvent nature. Tri-(aza-15-crown-5), tri- and hexa-(aminomethyl)-derivatives of 3,5-di-(arylmethylidene)-8-arylbicyclopentano[b,e]pyridine were synthesized with the main objective of subsequent study of their ion and pH-sensing properties. Generally, the synthesized bicyclopentano[b,e]pyridine derivatives are promising for their application as multi-purposes fluorescent probes.

Key words: dicyclopentano[b,e]pyridines; pH-sensors; fluorescence and NMR spectra; chemical synthesis; fluorescence probes.

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S
ynthesis of substituted benzo[c]furo[3,2-g]chromen-5-ones


Ya. L. Garazd, O. S. Ogorodniychuk1, M. M. Garazd1,
V. P. Khilya

Department of Chemistry, Taras Shevchenko National University (Kyiv)
64 Volodymyrska Str., Kyiv, 01033, Ukraine
1 Institute of Bioorganic Chemistry and Petroleum Chemisry, NAS of Ukraine
1 Murmanska Str., Kyiv, 02094, Ukraine

Abstract: Substituted benzo[c]furo[3,2-g]chromen-5-ones, the modified analogs of psoralen containing a benzene ring annelated at the 5,6-position of a furo[3,2-g]chromen-7-one system, were synthesized from 3-hydroxy-8-methoxybenzo[c]chromen-6-one.

Key words: coumarins, furocoumarins, psoralen, dibenzo[b,d]pyran-6-one, heterocyclization.

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S
earch for Ñasein Kinase 2 inhibitors among 4 aminoquinazoline derivatives


V. M. Sapelkin, A. G. Golub, O. Ya. Yakovenko,
V. G. Bdzhola, S. M. Yarmoluk

Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotny Str., Kyiv-143, 03143, Ukraine

Abstract: 75 compounds from combinatorial library of 4-aminoquinazoline derivatives have been chosen using receptor-based virtual screening technology for studying their CK2 inhibition activity. It has been shown that 9 substances inhibit CK2 activity by more than 70 %. IC50 of these compounds ranged from 7 to 20 μM. The most potent inhibitor, 1.57 (2-(3-methylphenyl)-4-(4-carboxyphenylamino)quinazolin, has IC50 7.7 μM.

Key words: CK2 inhibitors, 4-aminoquinazoline derivatives, receptor-based virtual screening.

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Inhibitors of protein kinase CK2

A. O. Prykhod'ko, G. G. Dubinina, S. M. Golovach,
S. M. Yarmoluk

Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotny Str., Kyiv-143, 03143, Ukraine

A
bstract: This review presents general data on the CK2 inhibitors of various chemical structure. Protein kinase CK2 (CK2) has long been implicated in the regulation of cell growth and proliferation. The CK2 negative role has also been proven in some mechanisms accompanying cell-controlled apoptosis (anti-apoptotic protecting function). Thus, the CK2 is considered as a perspective target for anticancer drugs. Our review presents the results of the search of CK2 inhibitors among known classes of the serinethreonine kinase antagonists: flavonoids, benzimidazole and benztriazole derivatives, aromatic sulfamides, fluoren and xantenone derivatives and others. The comparative analysis of CK2 inhibitors and their efficacy, specificity and probable mechanism of binding to active site has been done.

Key words: protein kinase, CK2, inhibitor, anticancer drugs.

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Onium salts as coupling reagents in the preparation of silica polymer supports for oligonucleotide synthesis

L. V. Dubey, I. Ya. Dubey

Institute of Molecular Biology and Genetics,
NAS of Ukraine
150 Zabolotny Str., Kyiv, 03143, Ukraine

Abstract: Two types of silica polymer supports for solid phase oligonucleotide synthesis were prepared using onium salts, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), in the presence of 1-hydroxybenzotriazole (HOBT) as activating reagents in the reactions of carboxylic functions with amino or hydroxy groups. The HBTU-HOBT system was found to be a more efficient coupling reagent for polyamide linker chain elongation and nucleoside attachment to the carboxylated silica support than the BOP-HOBT one.

Key words: oligonucleotides, polymer supports, coupling reagents, phosphonium salts, uronium salts.

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Secondary metabolites synthesis in transformed cells of Glycyrrhiza glabra L. and Potentilla alba L. as producents of radioprotective compounds

P. G. Kovalenko, V. P. Antonjuk1, S. S. Maliuta

Institute of Molecular Biology and Genetics,
NAS of Ukraine
150 Zabolotny Str., Kyiv-143, Ukraine
1Biospirtprod, Kyiv, Ukraine

Abstract: Following the Chernobyl explosion, screening for new drugs of radioprotective activity has been initiated in Ukraine. The European licorice (Glycyrrhiza glabra L.) is a pharmacologically important species which is rich in flavonoids and saponins, especially in the roots. To increase the pharmacological potential of this plant, the authors have obtained transformed licorice protoplasts with higher production of target compounds. Isolated licorice G.glabra L. protoplast suspension was electroporated by the chimeric plasmid pDNt23-CaMV35S-nos-npt-II-cat (pDNt23-root-specific and CaMV 35S promoters, nos-nopaline synthase terminator, and selectable NPT-II gene). On the selective medium with addition of kanamycine sulphate, proorganogenic clusters have been obtained. These obtained cell clusters have been additionly inoculated by Agrobacterim rhizogenes (15834). In general, the level of secondary metabolites in these transformed cells was 2-fold higher than in nontransformed control cells. We found that flavonoids isolated from transformed G.glabra cells possess aldose reductase inhibitory activities; these compounds have been tested on the rat lens. The intact root segments of Potentilla alba L. have been also inoculated by this strain too, to obtain «hairy roots» as terpens producent. These compounds have shown inhibitory effect on the thyroxine levels in white rat thyroid glands. These results suggested that metabolites obtained from transformed pharmaceutical plant species can be used as radioprotective compounds after γ-irradiation.

Key words: Glycyrrhiza glabra, Potentilla alba, foreign DNA, electroporation, hairy roots, radioprotectors.

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Search of potential aldose reductase inhibitors among 5-arylidene-4-oxothiazolidine-3-alkanoic
acids derivatives

R. B. Lesyk, B. S. Zimenkovsky, N. Y. Troc'ko1

Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv State Medical University, 69 Pekarska Str., Lviv, 79010, Ukraine
1Department of Organic Chemistry, Faculty of Pharmacy, School of Medicine, Staszica 6, 20-081 Lublin, Poland


Abstract: Aldose reductase, a member of the aldo-keto superfamily, is associated with several diabetic complications (retinopathy, cataracts, neuropathy and nephropathy). Aldose reductase inhibition is interesting as a tool permitting to prevent or delay the onset and to minimize the chronic diabetic complications. Orally active drugs — aldose reductase inhibitors, their mechanism of action, pharmacological activity and pharmacophore requirements are reviewed in this paper. A perspective of 5-substituted 4-oxothiazolidine-3-alkanoic acids as potential aldose reductase inhibitors has been discussed.
     Mild and efficient methods of 5-(2-methyl-3-phenyl-2-propenilidene)-2,4-dioxo-3-thiazolidinyl alkanoic acids synthesis are described. 2,4-Dioxothiazolidine potassium salt was coupled with ethyl chloroacetate to give corresponding ethyl ester, which was hydrolyzed in acid medium to yield the 2,4-thiazolidinedione-3-acetic acid (1). Condensation 1 with a-methylcynnamic aldehyde, according the Knoevenagel, gives 5-(2-methyl-3-phenyl-2-propenilidene)-2,4-thiazolidinedione-3-acetic acid (2), which is obtained alternatively by the reaction with N-potassium salts of 5-(2-methyl-3-phenyl-2-propenilidene)-2,4-thiazolidinedione and sodium chloroacetate. 4-(5-(2-Methyl-3-phenyl-2-propenilidene)-2,4-dioxo-3-thiazolidinyl)butanoic acids (3) has been synthesized by the α-butyrolactone alkylation of 5-(2-methyl-3-phenyl-2-propenilidene)-2,4-thiazolidinedione potassium salts. Synthesized heterocyclic acids 2,3 are gently converted into acid chlorides 4,5, which reacted with aromatic amines to yield corresponding amides 6—13. Biological activity prediction using computer program PASS C&T has been made.

Key words: aldose reductase inhibitors, 2-thioxothiazolidones-4,5-(2-methyl-3-phenyl-2-propenili-
dene)-2,4-dioxo-3-thiazolidinyl alkanoic acids, synthesis.

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Do mammals die young!? An age-dependent mechanism of mammals self-destruction

O. G. Boyko

Multi-Branched Centre of Science & Technology «Agrobiotech»
50 Kharkivski highway, Kyiv, 02160, Ukraine


Abstract: It is hypothesized that, in the evolutionary lineage from the mammal-like reptiles Synapsida to mammals, in addition to existing systemic and cellular mechanisms of aging arising appears particular age-related mechanism of self-destruction of organism mammals, which does not allow accumulation of individuals with the damage of genome in population. Age-related mechanism of self-destruction of organism mammals is a result of the evolutionary events linked with arising of phenomenon "postmitotic brain" in mammals

Key words: aging, hypothesis, mammals, birds, exogenous organospecific RNAs, postmitotic brain.

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