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Introduction. The structure of dihydroquercetin (DHQ) is characterized by two chiral centers at positions 2 and 3 of the benzopyran cycle, resulting in possible diastereomers: trans- and cis-isomers. Therefore, the development of methods for qualitative and quantitative control of DHQ diastereomers in analyzed samples is essential for patient safety management. Nuclear magnetic resonance (NMR) spectroscopy is one of the physicochemical methods that can be used for this purpose.Aim. The study objective was to accumulate the analytical and structural characteristics of cis-DHQ by NMR spectroscopy of the spheroidal form of this flavonoid (DHQs).Materials and Methods. 1D 1H, 1H,1H-COSY, 1H,1H-NOESY, and 1H,13C-HSQC NMR spectra were acquired at 298 K on an 800 MHz NMR spectrometer equipped with a TXI triple resonance probe. The number of scans was 32. The mixing time in the NOESY experiment was 400 ms. The 1H and 13C were analyzed using CcpNmr software. The dihedral angles were calculated by applying the Karplus equation.Results and discussion. In trans-DHQ, the chemical shift values for H2 and H3 are 4.93 ppm and 4.52 ppm, respectively, and in cis-DHQ they are 5.31 ppm and 4.20 ppm, respectively. The spin-spin coupling constants between H2 and H3 of trans- and cis-DHQ are 12.00 Hz and 2.40 Hz, respectively. Thus, the dihedral angles for the trans- and cis-isomers are 154° and 64°, respectively. We found that DHQs contains 12.5 % of the cis-isomer.Conclusion. Our experiments confirmed that NMR spectroscopy can discriminate between trans- and cis-DHQ based on the chemical shift values for the cross-peaks of H2 and H3. The second major finding was that this method can be considered as a more selective quantitative analysis than HPLC with UV detection without reference. One of the most important results of this study for drug development is the updated information on the structural parameters of DHQ diastereomers in the liquid phase.

The biochemical approach for age assessment is most appropriate in forensic medicine, as racemization of aspartic acid in bones and teeth is closely related to human biological age. The aim of the study is to assess the biochemical parameters of aspartic acid in human teeth, which can be implemented into forensic practice in Russia. Samples of dentin in amount of 20, taken from the teeth of subjects aged between 16 and 76, were examined. Chromatographic analysis of the samples was performed on a gas chromatograph using chiral column. Statistical data processing showed that the relative squared peak of D-aspartic acid has a strong correlation with human biological age. Data, obtained from the Russian population study, demonstrate the applicability of chromatography for forensic purposes. It should be noted that the approach to the racemization rate estimation in the hard tooth tissue was performed using standard laboratory equipment, which allows to easily implement this method in forensic medical practice.

α-Lipoic acid (also known as thioctic acid) is a natural vitamin-like compound. Lipoic acid contains asymmetrical carbon, which causes the presence of two possible optical isomers (enantiomers): R-lipoic acid (levogyrate isomer) and S-lipoic acid (rightspinning isomer). Lipoic acid functions as a cofactor for several important mitochondrial multienzyme complexes, enhances the uptake of glucose by the cells, and modulates the activity of various signaling molecules and transcription factors. It was shown that α-lipoic acid and its derivative, dihydrolipoic acid, have a direct antioxidant effect due to the neutralization of reactive oxygen species that are destructive to DNA, proteins and lipids of cells. Dihydrolipoic acid enhances the antioxidant properties of ascorbic acid, glutathione and ubiquinone. Available evidence suggests that supplementation with lipoic acid reduces the symptoms of peripheral diabetic neuropathy. Results from randomized controlled trials show that high doses of lipoic acid can improve the glycemic profile of subjects with metabolic disorders. Lipoic acid can be used to control body weight in people with obesity. R-Lipoic acid is synthesized in the human body and is contained in foods in a form covalently associated with lysine (lipoyllysine). Its dose in dietary supplements significantly exceeds the amount in the diet. Most dietary supplements contain a racemic mixture of R- and S-lipoic acid., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

A novel promising strain of actinobacteria Rhodococcus sp. 77-32 was identified. Its acetonetreated biomass the could be used as a biocatalyst for production of S-(-)-2-[6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl] ethanol (S-BCE), a precursor of natural α-tocols. It was established that a reaction of enantioselective hydrolysis of racemic (±)-2-(2-acetoxyethyl)-6-benzyloxy-2,5,7,8-tetramethylchroman (BCEA) occurred in the phosphate buffer–acetone system, resulting in enrichment of the residual substrate by S-enantiomer (S-(+)-2-(2-acetoxyethyl)-6-benzyloxy-2,5,7,8-tetramethylchroman, S-BCEA). It was shown that the hydrolysis was accompanied by stereoinversion of the formed product, R-(+)-2-[6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl] ethanol (R-BCE), into the S-BCE. The transformation conditions (acetone content, acidity, temperature, reaction duration) were optimized, providing simultaneous production of optically pure S-BCE and S-BCEA with an almost quantitative yield.

Earlier unknown enantiomerically pure (R)- and (S)-1,8-diamino-3-methyl-4-azaoctane's (3-MeSpd's) were synthesized with high overall yields and optical purity starting from commercially available R- and S-isomers of N-Boc-2-aminopropanol-1. Application of R- and S-isomers of 3-MeSpd for the investigation of the stereospecificity of spermidine transporter and peculiarities of deoxyhypusine synthase reaction are discussed.

The conditions of the formations of trans isomers of fatty acids, depending on the method of processing and storage of the raw material of microbial, plant and animal origin, were investigated. In the composition of lipids, except for the main trans-isomer elaidic acid, nonsignificant amounts of trans-2-hexen-4-ynal, trans-2-formlcyclopro-panecarboxylate, methyl octadeca-9-yn-l1-trans-enoate, trans-2, 2-dimethyl-3-(2-propenyl)-ethyl ester, trans-9-octadecenoic acid, and trans-1,5-heptadiene, and mixed isomers of methyl-octadeca-9-yn-1-trans-enoate, methyl-9-cis, 11-trans-octadecadienoate, 1-[trans-4-(2-iodo-ethyl) cyclohexyl]-trans-4-pentylcyclo-hexane and cis-9, and trans 11-octadecenoic acid. The major trans elaidic acid component was detected in natural objects of different origin in quantities not exceeding 0.05-0.11%. The combination of thermal processing with other parameters, especially enzymatic treatment, led to an increased proportion of trans isomers. The content of trans isomers is usually proportional to the time of storage of materials.

In previous work we have obtained a dimeric dipeptide mimetic of 4th loop of BDNF - hexamethylenediamide bis-(N-monosuccinil-L-seryl-L-lysine) (GSB-106), having a neuroprotective activity in vitro in a concentration range 10(-5)-10(-8) M and an antidepressant activity in vivo at doses 0.1 and 1 mg/kg i.p. in rats. We have investigated the structural and functional relationships among analogues of GSB-106. Glycine scan was performed and a number of appropriate compounds were synthesized: GT-105 (here lysine is replaced by glycine), GT-107 (here serine is replaced by glycine), GT-106Ac (here monosuccinic radical is replaced by acetyl group). We have studied the dependence of activity of following compounds from the configuration of amino acid residues: GT-107D (D-enantiomer of the GT-107), GT-106DL (L-serine was replaced by D-serine), GT-106LD (L-lysine was replaced by D-lysine). The investigation of these compounds using the HT22 cell culture in conditions of oxidative stress has approved only two analogues of GSB-106 to have a neuroprotective effect: in the case of replacement of serine to glycine and of replacment of succinic radical to acetic group. A disappearance of this effect was observed in event of the replacement of lysine residue to glycine in GT-105, L-lysine residue to D-lysine and also by conversion of serine configuration. These results show that lysine residue is crucial for the neuroprotective activity of GSB-106. L-Configuration of the lysine and serine residues required. Configuration of lysine residue becomes critical in absence of serine side group. Thus, the the following fragment is a minimum pharmacophore of beta-turn of 4 loop of BDNF: HOOC-CH2-CH-CO-NH-(S)-CH(CH2OH)-CO-NH-(S)-CH((CH2)4NHz)-CO-NH-(CH2)3-. Only one (GT-106Ac) out of two analogues of GSB-106 with neuroprotective activity possesses antidepressant activity too. This fact indicates about a necessity of more stringent structural requirements for exposure of antidepressant activity. The results obtained can be useful for designing of new active mimetics of BDNE

The aim of the study was to perform isomeric analysis of hydroxyeicosatetraenoic acid (HETE) in blood samples from obese patients with non-alcoholic (NASH) and alcoholic (ASH) steatohepatitis. Sixty nine obese patients with liver steatosis according to abdominal US data and chronic ALT elevation were assign into two groups aecoriing to the evaluation of alcohol consumption by GAGE and AUDIT questionnaires: NASH - 39 patients and ASH - 30 patients. The identification and quantification of 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 15-HETE and also non-enzymatic oxidation product 11-HETE in blood plasma were carried out by HPLC-MS-TOF with using 2-hydroxyoctanoic acid as internal standard. The position of hydroxyl group in HETE was elucidated by HPLC-MS/MS. The MS/MS transitions were for 15-HETE m/z 319 ---> m/z 219; for 11-HETE m/z 319 --> m/z 167; for5-HETE m/z 319 --> m/z 115. Patients' body composition was evaluated by bioelectrical impedance, resting energy expenditures (REE) were assessed by indirect calorimetry and nutrition pattern was examined by foodfrequency questionnaire. Mean age, BMI and ALT serum level were similar in patients from ASH and NASH groups. Blood plasma 8+12-HETE concentration was also similar in both groups of patients, but concentration of 15-HETE (21,6±20,2 vs 11,9±13,7µg/ml, p =0,02) and 11-HETE (20,8±21,3 vs 11,2+12,9 ug/ml, p =0,03) was significantly higher in NASH patients. ASHpatients demonstrated higher lean body mass (68,1±10,6 vs 57,9±9,8 kg, p<0,001) and muscle mass (39,3±6,1 vs 33,2±6,8 kg, p<0,04) and higher rate of protein oxidation (98,5±3 1 vs 76,2±21,1 g/day, p= 0,02) recalculated from REE. There were no differences found in blood lipids content as well as in consumption of total dietary fat, however, there was a trend to difference in saturated/unsaturated fatty acids ratio between groups (2,3±0,2.in NASH and 1,4±0,3 in ASH patients). In conclusion, the rate of production of eicosatetraenoic acid metabolites by lipoxygenase pathway is different in NASH and ASH overweight patients. It means that possibly different mechanisms are responsible for formation of potentially toxic fatty acids metabolites in these two types of patients. It seems likely that differences in fatty acids consumption pattern are related to this metabolic pathway.

Two diastereomers of methylpheophorbide a 13(2)-N-n-octyl-N-(2-hydroxy-3-isobornyl-5-methylbenzyl)amide were obtained from (+)- and (-)-enantiomers of 2-isobornyl-4-methylphenol. Evaluation of membrane protective and antioxidant activity of individual diastereomers on the model of H2O2-induced hemolysis of blood erythrocytes showed that the stereochemistry of isobornyl substituent in the synthesized conjugates has no effect on their biological activity.

A synergetic law, being of common physicochemical and biological sense, is formulated: any evolving system that possesses an excess of free energy and elements with chiral asymmetry, while being within one hierarchical level, is able to change the type of symmetry in the process of self-organization increasing its complexity but preserving the sign of a prevailing chirality (left - L or right - D twist). The same system tends to form spontaneously a sequence of hierarchical levels with alternating chirality signs of de novo formed structures and with an increase of the structures relative scales. In living systems, the hierarchy of conjugated levels of macromolecular structures that begins from the "lowest" asymmetric carbon serves as an anti-entropic factor as well as the structural basis of "selected mechanical degrees of freedom" in molecular machines. During transition of DNA to a higher level of structural and functional organization regular alterations of the chirality sign D-L-D-L and L-D-L-D for DNA and protein structures, respectively, are observed. Sign-alternating chiral hierarchies of DNA and protein structure, in turn, form a complementary conjugated chiral pair that represents an achiral invariant, that "consummates" the molecular-biological block of living systems. The ability of a carbon atom to form choral compounds is an important factor that determined carbon basis of living systems on the Earth as well as their development though a series of chiral bifurcations. The hierarchy of macromolecular structures demarcated by the chirality sign predetermined the possibility of the "block" character of biological evolution.

The effect of Acholeplasma laidlawii var. granulum 118 on activity of phenylalanine-ammonia-lyase (PAL) in callus cultures of sugar beat was researched. The optimal conditions of enzyme reaction were: using the L-phenilalanine as a substrate, pH 8.4-8.8, the temperature optimum 38-40 degrees C. It was established that at the infecting of sugar beat callus culture by phytopathogenic mollicute the PAL activity was temporarily increased and reached its maximum after 2 h of infecting. Then it gradually decreased and in 24 h reached its initial level. An increase of PAL activity of plant is considered as protective reaction in response to the action of pathogen.

Molecules of dissolved substance in many homochiral solutions are arranged in linear associations forming chiral strings (with length to diameter proportion of 10(1)-10(5)), which leads to solidification of the solution into anisometric gel. This paper describes the formation of the string system in aqueous solution of amino acid phenylalanine, formation of individual strings, weaving of thin strings into thick ones, successive alteration of the solution chirality sign with transition to new levels of the association organization. It seems that biological media are anisometric fluids containing chiral molecular associations and strings, or anisometric gels.

Electroconductive interpolymer polyaniline complexes are synthesized on the DNA matrix, using the method of oxidative polymerization of aniline with two different biocatalyzers: horseradish root peroxidase and micropiroxidase-11 biomimetic. The spectral characteristics and morphology of the acquired biocomposites have been studied. The stereospecificity of the acquired samples of interpolymer complexes is shown, depending on the biocatalyzers used. The results acquired indicate the important role of a biocatalyzer in the formation of the twist direction of an electroconductive polymer spiral on the DNA matrix; i.e., the optical activity of the polymer samples acquired is apparently associated with the biocatalyzer properties.

Luminescence and excitation spectra of the highly luminescent stacking dimers of adenine and uracil in water solutions are studied. By the luminescence excitation spectra method it is shown that the stacking aggregates of adenine and uracil are formed with participation of rare forms of monomer molecules: N7H tautomers of adenine and the uracil molecules in rare forms of hydratation, for example molecules without H-bonds with water. The study of temperature dependence of luminescence intensity of monomers and stacking dimers of uracil has shown that stacking dimers do not dissociate even at 85 degrees C similarly as described earlier for adenine and adenosine. Stable stacking aggregates of nucleic bases are most likely to be the precursors of RNA molecules in chemical evolution. This hypothesis is supported by new data on their stability.

This study was aimed at a comparative analysis of the effects of new amino acid derivatives of dopamine (IEM-2111, IEM-21122, IEM-2123, IEM-2126) on anxiety-like behavior in rats. The behavioral effects of the dopamine-like substances were evaluated under conditions of acute and chronic experiments. In acute experiment, a single dose of substances was administered 45 min prior to the behavioral testing of animals. In chronic experiment, the synthesized compounds were administered in a single daily dose for 14 days. Pharmacological analysis of the effect of drugs was performed in the following doses: 0.1, 1.0, and 10.0 mg/kg (i.p., introduction). Diazepam was used as a reference drug that was introduced in a dose of 1.0 mg/kg (i.p.). The anxiety-like state was determined using the elevated plus maze test, while the behavioral effects were evaluated in the open field test. It was found that IEM-2111, IEM-2122, and IEM-2123 exhibited anxiolytic action under condition of chronic administration, whereas IEM-2126 produced an anxiolytic effect only after acute administration. The introduction of left optical isomers of aromatic or heterocyclic radicals of amino acids into the molecule of 3,4-dimetoxyphenylethylamine results in a more pronounced anxiolytic effect upot chronic administration. The degree of action of the new amino acid derivatives of dopamine has a dose-dependent character, and the maximum effect is manifested at a dose of 1.0 mg/kg.

We conducted a comparative study on the effect of active compounds of pantogam and pantogam active (calcium D(R)-homopantothenate and calcium DL(RS)-homopantothenate) and its L(S)-isomer on the receptors of main brain neuromediators in rats using in vitro radioligand binding analysis. All three compounds interact with binding sites of specific GABA-A and, in particular, GABA-B receptor ligands. Racemate and S-enantiomer, but not its R-form, competed to a moderate degree for D2-receptor binding sites. In all cases, degrees of interaction with receptors were ranged as follows: S-isomer>racemate>R-isomer. These qualitative and quantitative differences are assumed to contribute to pharmacological activity of both drugs.

Structural characteristics of ibuprofen substances manufactured by different firms and the impact of micronization on them were compared. The study showed that the use of X-ray diffraction methods was necessary for certification of medicinals (crystalline) since only such methods provided information on the substance crystal structure, the molecular state and polymorphous forms.

Features of the hypothetical evolution of a hierarchy of chiral objects formed by active media are discussed. On the basis of experimental facts a new synergetic generalization is made: an evolving system can repeatedly broaden the spectrum of its symmetry types within one level of organization which increases its complexity and change the sign of chirality during transition to a higher level. Switching the chirality sign of macroscopic objects provides irreversibility of stratification. The known chirality of biological structures at different levels suggests that the chiral L/D-stratification should be universal and the hierarchical paths are stable and determined. A high level enantiomorph with reciprocal chirality demonstrates a wider spectrum of functionality. A fractal description of natural hierarchical systems is pointed out to be inadequate because it implicates invariance of the chirality sign of the objects at different scales.

The resolution of the racemic ortho-isobornylphenol into enantiomers via diastereomeric camphanates was carried out. The absolute configuration ofchiral centers of synthesized compounds was established by the single crystal X-ray diffraction method. Antioxidant activity and membrane protective properties of individual enantiomers were studied on the model of H2O2-induced hemolysis of red blood cells.

9alpha-Hydroxy derivatives were prepared from 11 steroids ofandrostane and pregnane series using Rhodococcus erythropolis VKPM Ac-1740 culture with 0.5-20 g/l substrate concentration in the reaction mixture. 9alpha-Monohydroxylation proceeded regardless of the substituent structure at C17. However, the structure of the steroid molecule influenced the time of complete conversion of the substrate and the yield of the transformation product. 9alpha-Hydroxy-androstenedione was obtained in 35 h in a yield of 85% when the maximum concentration of androstenedione (AD) was 10 g/l. 9alpha-Hydroxy-AD was also formed by the actinobacterium cells entrapped in poly(vinyl alcohol) cryogel beads. Nine successive transformation cycles were carried out using immobilized cells at 4.0 g/l concentration of AD in the medium. The yield of 9alpha-hydroxy-AD formed during six cycles (from two to eight with the duration of each cycle for 22-24 h) was 98%.

We compared the efficiency of different stereoisomers of organic magnesium salts (Mg DL-, Mg D-, and Mg L-aspartate and Mg L- and Mg DL-glutamate) after oral administration under conditions of furosemide-induced magnesium deficiency. The time to complete compensation of erythrocyte magnesium level was 5 days for Mg L-aspartate, 10 and 8 days for Mg L-glutamate and Mg D-aspartate, respectively, and 11 days for Mg DL-aspartate and Mg DL-glutamate. These findings attest to better bioavailability of Mg complex with L-stereoisomer of aspartate in comparison with DL and D-stereoisomers and stereoisomers of Mg glutamate.

The paper covers investigation of cytogenetic activity of chiral mutagens and their specific effects on the plant cells chromosomes of soft winter wheat (Triticum aestivum L.). Comparative analysis of cytogenetic activity of chiral NEU: S(+)1-N-nitroso- 1-N-methyl-3-N-sec-buthylureas (S(+)NMsBU) and R(-)1-N-nitroso- 1N-methyl-3-Nsec-buthylureas (R(-)NMsBU) on winter wheat was performed. As it was shown by the frequency of chromosomal aberrations the S(+) stereoisomer was twice more active than R(-). In addition to typical anaphase aberrations (fragments, bridges, lagging chromosomes) the numerous mitosis pathologies were revealed - K-mitoses, hyperspiralization and despiralization of chromosomes, unequal allocation of chromosomes between the daughter nuclei, mass fragmentation, nondisjunction and chromosome adhesion, three-pole mitoses, etc. Neither of the mentioned pathologies was observed under the action of NEU and gamma-rays.

The features of monovalent and bivalent binding of receptors (or antibodies) with a polyvalent ligand (or with an antigen) are considered. It is shown that the rigid connection of the binding sites of the receptor brings to high increase of binding affinity for the corresponding ligand, but only in case if its epitopes are fully complementary to both sites of the receptor binding. If not, then there is no advantage of the binding of bivalent receptor before univalent binding. If the binding sites of the receptor are connected by a flexible linker, then regardless of location of epitopes of the corresponding ligand there is the successful fastening of receptor and ligand. Exactly the connection by a flexible linker is used by Nature in most cases at constructing of polyvalent receptors.

L-[methyl-(11C)]-methionine ([11C]MET), labelled with carbon-11 (T1/2 = 20 min), is the most commonly used amino acid radiotracer for PET diagnostics of brain tumors. The production of [11C]MET via on-line 11C-methylation of L-homocysteine thiolactone hydrochloride (lactone) on C18 solid-phase extraction cartridge creates a problem of insufficient enantiomeric purity (content of L-isomer) of the product. The results of a systematic study of the influence of reaction parameters (lactone/base and the EtOH/H20 ratios, time of 11C-methylation) on the content of L-isomer in the preparation are presented. The developed method of on-line [11C]MET synthesis allows to obtain a product with a sufficiently high radiochemical yield (75 +/- 3%, n = 100, based on [11C]CH3I) and reliably high content of L-isomer (93.7 +/- 0.5%) satisfying the requirements of clinical applications. [11C] MET synthesis was performed on a fully automated module designed by the Institute of Human Brain (IHB RAS).

Verapamyl substance and market verapamyl were investigated with circular dichroism. It was shown that circular dichroism provided rapid and highly efficient determination of the optic isomers and could be recommended as a method for control of drug quality.

Four polyhydroxylated steroids, new (20R)-5alpha-cholestan-3beta,6alpha,8,15alpha,24,26-hexaol (I) and known (20R,25S)-5alpha-cholestan-3beta6alpha,8,15beta,16beta,26-hexaol, (20R,25S)-5alpha-cholestan-3beta,6alpha,15beta,16beta,26-pentaol, and marthasterone sulfate were isolated from the Solaster endeca starfish inhabiting the Sea of Okhotsk and characterized. Steroid (I) contains a 24,26-dihydroxylated side chain, which is uncommon for starfish polyols. The isolated steroids and related metabolites from two starfish species of the Evasterias genus (in total, 15 compounds) were weakly cytotoxic in a human HeLa cell culture and some of them were inhibitors of nonspecific esterase from mouse Ehrlich carcinoma. The effects of these compounds on the p53 protein activity were studied in a yeast two-hybrid test system and both inhibitors and stimulators of this activity were found among them.

Under the action of PCl(5), the Beckman rearrangement of a 3 : 1 mixture of Z- and E-ketoximes of 18beta-hydroxydihydroquinopimaric acid resulted in 5'-caprolactam and isomeric caprolactams containing fragments of cyclic ether. Z- and E-ketoximes were separated as acetates. Using a carrageenan inflammation model, we demonstrated that the anti-inflammatory activity of quinopimaric acid derivatives was comparable with that of diclofenac.

Possible pathways by which brassinosteroids affect the monooxygenase enzymatic system of mammalian liver microsomes, which is involved in the transformation of a broad spectrum of xenobiotics, were studied. The role of the structure of the side chain of brassinosteroids in the regulation of monooxygenase activity was studied using two natural compounds (24-epibrassinolide and 28-homobrassinolide) and two synthetic analogues, (22S, 23S-dihydroxy) stereoisomers. The results of this study show that brassinosteroids can directly influence the functioning of the microsomal enzymatic system. It was found that the degree of this influence depends on the side chain structure. This suggests the possibility of targeted modification of natural compounds to ensure the desired physiological effects.

Unique stereochemistry of the third-generation beta-adrenoblockers is a basis of advantages of the new drugs such as carvedilol. Data on the stereochemistry beta-adrenoblockers and the influence of their optical activity on the pharmacological effects of related drugs are presented. Main steps in the practical invest gation of carvedilol stereoisomers are reviewed. Clinical aspects of the use of carvedilol, representing a racemic mixture of two enantiomers, in the treatment chronic heart failure, arterial hypertension, and coronary heart disease are considered.

A reaction of high-temperature solid-phase catalytic isotope exchange (HSCIE) was studied for the preparation of tritium- and deuterium-labeled ligands of glutamate and dopamine receptors. Tritium-labeled (5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclopenten-5,10-imine ([G-(3)H]MK-801) and R(+)-7-hydroxy-N,N-di-n-propyl-2-aminotetraline ([G-(3)H]-7-OH-DPAT) were obtained with a specific activity of 210 and 120 Ci/mol, respectively. The isotopomeric distribution of deuterium-labeled ligands was studied using time-of-flight mass-spectrometer MX 5310 (ESI-o-TOF) with electrospray and orthogonal ion injection. Mean deuterium incorporation per ligand molecule was 11.09 and 3.21 atoms for [G-(2)H]MK-801 and [G-(2)H]-7-OH-DPAT, respectively. The isotope label was shown to be distributed all over the ligand molecule. The radioreceptor binding of tritium-labeled ligands [G-(3)H]MK-801 and [G-(3)H]-7-OH-DPAT was analyzed using the brain structure of Vistar rats. It was demonstrated that [G-(3)H]MK-801 specifically binds to hippocampus membranes with K(d) 8.3 +/- 1.4 nM, B(max) being 3345 +/- 300 fmol/mg protein. The [G-(3)H]-7-OH-DPAT ligand specifically binds to rat striatum membranes with K(d) 10.01 +/- 0.91 nM and B(max) 125 +/- 4.5 fmol/mg protein. It was concluded that the HSCIE reaction can be used for the preparation of highly tritium-labeled (+)-MK-801 and 7-OH-DPAT with retention of their physiological activities.

Three new steroid glycosides (evasteriosides C, D, and E), along with six known compounds, were isolated from two Pacific starfish of the genus Evasterias. Evasterioside C from E. retifera collected from the Sea of Japan was identified as (20R,22E)-3-O-(beta-D-xylopyranosyl)-24-nor-5alpha-cholest-22-ene-3beta,6beta,8,15alpha,26-pentaol 26-sulfate sodium salt. The structures of evasterioside D and E from E. echinosoma (collected from the Gulf of Shelichov, the Sea of Okhotsk) were established as (20R,24S)-24-O-(beta-D-glucopyranosyl)-5alpha-cholestane-3beta,6alpha,8,15beta,24-pentaol and (20R,24S)-3,24-di-O-(beta-D-xylopyranosyl)-cholest-4-ene-3beta,6beta,8,15alpha,24-pentaol, respectively. In addition, the known compounds pycnopodiosides A and C, luridoside A, 5alpha-cholestane-3beta,6alpha,8,15beta,16beta,26-hexaol, 5alpha-cholestane-3beta,6alpha,8,15beta,24-pentaol 24-sulfate sodium salt, and marthasterone sulfate sodium salt were identified in E. echinosoma. The structures of the isolated compounds were established on the basis of spectroscopic analyses using 1D and 2D NMR techniques, mass spectrometry, and some chemical transformations.

An improved method for the synthesis of 3-deoxy-3-carboxymethylnucleosides was suggested. Oxidation of 5-O-benzoyl-l,2-O-isopropylidene-alpha-D-xylofuranose resulted in the 3-keto derivative, which was treated with triethylphosphonoacetate in the presence of sodium hydride to obtain the 3-deoxy-3-ethoxycarbonylmethylene derivative. Hydrogenation of the unsaturated compound proceeded strictly stereospecifically and gave the product with the ribo configuration. Acetolysis of the resulting compound with AcOH-Ac2O-CH3SO3H led to 1,2-di-O-acetyl-5-O-benzoyl-3-deoxy-3-ethoxycarbonylmethyl-D-ribofuranose, whose interaction with persilylated nucleic bases gave 3-deoxy-3-ethoxycarbonylmethylnucleosides in a total yield of 42-49% from the starting compound.

Preparations with different contents of thermolysin were obtained by the immobilization of the enzyme on granulated polyvinyl alcohol cryogel. Their activity and stability in an aqueous medium and in mixtures of polar organic solvents of different composition were investigated. The catalytic properties of the preparations in reactions of peptide bond formation were studied, and the optimal amount of the biocatalyst, the concentrations of initial reagents, and the ratios of organic solvents and water necessary for effective enzymatic peptide synthesis catalyzed by immobilized thermolysin were determined. A series of peptides of the general formula Z-Ala-Ala-Xaa-pNA, where Xaa = Leu, Ile, Phe, Val, or Ala, were synthesized, and the immobilized enzyme was shown to retain substrate specificity in an organic medium.

Methods of stereoselective synthesis of oxysterols are considered by the examples of (25R)-26-hydroxycholesterol, (24S)-24,25-epoxycholesterol, and (24S)-24-hydroxycholesterol containing functional groups in the terminal fragments of their side chains. Special attention is paid to the problems of construction of chiral centers C24 and C25.

Novel synthetic oxysterols (22S,23S)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one (I) and (22R,23R)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one (II) influenced cholesteryl esters biosynthesis in human hepatoma Hep G2 cell line from [14C]acetate (85% and 180% compared to control at the concentrations of 5 microM). The level of cholesteryl esters biosynthesis in Hep G2 cells from [14C]oleate increased in the presence of ketosterol (I) in a dose dependent manner, whereas the level of cholesteryl esters biosynthesis in the presence of ketosterol (II) reached the maximal value (269+/-20% from control) at the concentration of 1 microM. In a cell free system ketosterol (I) increased the rate of ACAT-dependent cholesterol acylation like 25-hydroxycholesterol, however, ketosterol (II), efficiently stimulating initial rate of ACAT-catalyzed cholesterol esterification, caused in rapid inactivation of this enzyme.

Oligonucleotide analogues bearing an acyclocytidine linked to thymidine by an amide (3'-O-CH2-CO-N-5') bond were synthesized. Melting curves of duplexes formed by modified oligonucleotides and complementary natural oligomers were obtained and thermodynamic parameters of their formation were measured. Replacement of dCpT by a modified dinucleotide only moderately decreased the melting temperature of these modified duplexes in comparison with unmodified duplexes containing complementary natural bases. CD spectra of modified duplexes were studied, and the duplex spatial structures are discussed. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.

We treated with nucleophiles derivatives of chlorophyll a with additional six-membered cycles: delta-lactone at pyrrole D and anhydride at pyrrole C bearing a gamma-meso-bridge. In the first case, this led to the formation of substituted amides at the propionic acid residue and the introduction of hydroxy group at position 18 of the macrocycle, and, in the second case, to N-substituted cycloimides of chlorin p6. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru

The synthesis of retinal analogue series that contain a spyropyran moiety instead of a trimethylcyclohexene ring was proposed. The process of the retinal analogue interaction with bacterioopsin from apomembranes of Halobacterium salinarum and the spectral properties of the newly formed pigments were studied. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.

Chemical synthesis of a series of modified oligodeoxyribonucleotides containing one or two residues of thymidine glycol (5,6-dihydro-5,6-dihydroxythymidine), the main product of oxidative DNA damage, is described. The thermal stability of DNA duplexes containing thymidine glycol residues was studied using UV spectroscopy. Introduction of even one thymidine glycol residue into the duplex structure was shown to result in its significant destabilization. Data on the interaction of DNA methyltransferases and type II restriction endonucleases with DNA ligands containing oxidized thymine were obtained for the first time. Introduction of a thymidine glycol residue into the central degenerate position of the recognition site of restriction endonuclease SsoII was found to result in an increase in the initial hydrolysis rate of the modified duplex in comparison with that of the unmodified structure. The affinity of C5-cytosine methyltransferase SsoII for the DNA duplex bearing thymidine glycol was found to be twofold higher than for the unmodified substrate. However, such a modification of the DNA ligand prevents its methylation. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.

Aim of the study was to assess effect of therapy with b-adrenoblockers and If-inhibitors on the rate of development of coronary complications of carotid endarterectomy. Patients (n=111, mean age 61 +/- 4 years) subjected to carotid endarterectomy in 2006 - 2007 were divided into 3 groups according to therapy in pre-, intra-, and postoperative period. Group 1 consisted of 48 patients treated with metoprolol. Group 2 comprised 33 patients with contraindications to b-adrenoblockers who were treated with If-inhibitor ivabradine. Patients of control group 3 (n=30) received neither b-adrenoblocker nor If-inhibitor. There were no significant differences between groups in sex, age, concomitant pathology, and degree of stenosis of operated carotid artery. We assessed rate of development of ischemia and myocardial infarction during operation and in first 24 hours after surgery. In group 1 mean 24 hour heart rate according to Holter ECG monitoring after 7 days of therapy decreased by 14 +/- 3,7 beats/min, episodes of ischemia after surgery were registered in 4 patients (8%). In group 2 mean 24 hour heart rate decreased by 10 +/- 2,5 beats/min, 4 patients (12%) had signs of myocardial ischemia during first 24 hours after surgery. There were no myocardial infarctions in groups 1 and 2. In control group mean 24 hour heart rate did not significantly change. Significantly higher number of postoperative coronary complications was revealed among patients of this group: 2 (6%) developed myocardial infarctions, in 5 (17%) appeared signs of myocardial ischemia. Administration of b-adrenoblocker metoprolol and If-inhibitor ivabradine significantly lowers rate of development of coronary complications after carotid endarterectomy. Ivabradine is indicated to patients with contra indications to b-adrenoblockers.

Aim: To assess ivabradin and nebivolol efficacy in combined treatment of ischemic heart disease patients with chronic heart failure (CHF) of functional class (FC) II-III by NYHA, impact of these drugs on quality of life, circadian indices of myocardial ischemia (CMI), left ventricular (LV) contractility., Material and Methods: A total of 92 patients with CHF of FC II-III (mean age 57.3 +/- 4.5 years) were randomized into 3 groups. Patients of group 1 (n = 30) received combined basic therapy: inhibitors of ACE, diuretics, aspirin, statins, on demand nitrates. Patients of group 2 (n = 33) received basic combined treatment plus nebivolol (nebilet, Berlin-Chemie/Menarini) in a dose 5.0 mg/day. Group 3 (n = 29) was given basic therapy plus ivabradin (coraxan) in a mean dose 7.5 mg., Results: The addition of ivabradin and nebivolol to combined treatment of ischemic heart disease with LV dysfunction brought about control over heart rate (HR), improved quality of life, reduced severity of CHF, CMI, number of episodes of painful and painless ischemia. In reduced by nebivolol HR addition of ibavradin improved systolic and diastolic LV function. The analysis of HR variability in ivabradin administration showed enhancement of parasympathic activity in the vegetative balance. Administration of nebivolol produced modulated attenuation of sympathic activity., Conclusion: Addition of ivabradin and nebivolol to combined treatment of ischemic heart disease with LV dysfunction raises efficacy of treatment.

A tritium-labeled C-terminal fragment of dermorphin (H-Tyr-13,4-3HJPro-Ser-NH2) and its isomer (H-Tyr-D-[3,4-3H]Pro-Ser-NH2) with molar radioactivity of 35 Ci/mmol were synthesized, and their pharmacokinetics and metabolism in rat organs were studied after their intramuscular injections. The tripeptides were detected in the blood only for 5 min after the injection, and maximum contents of both compounds (approximately 5% of the total amount of the injected label) were registered in the kidneys after 20 min. Both stereomers were shown to penetrate into the brain. We failed to detect any radioactive metabolite, except proline, due to rapid proteolytic degradation of these peptides.