Cis-trans isomerization in cyclosporin C dissolved in acetonitrile.

Cyclosporin is an 11-amino acid cyclic peptide with pharmacologically valuable properties which has a variety of actual and potential applications. Its activity relies on the cell membrane permeability which, in turn, depends on the structure of cyclosporin and its ability to change the conformation. In this work, conformational exchange processes occurring in cyclosporin C were studied using one- and two-dimensional nuclear magnetic resonance spectroscopy. The free energy barrier separating two major conformers observed in polar solution (acetonitrile) was found to be 77 ± 2 kJ/mol. Less populated conformation states are also present in the solution, which agrees with the ease of formation of multiple forms revealed by MD simulations of cyclosporin C.

Comparison of cyclosporin variants B-E based on their structural properties and activity in mitochondrial membranes.

Cyclosporins B, C, D, and E were characterized by NMR spectroscopy, and backbone flexibility was studied by molecular dynamics simulation. Structures of the molecules were characterized by nuclear Overhauser effect spectroscopy, which revealed that the studied peptides have many common features. Molecular dynamics simulation showed that the backbone of cyclosporin E is relatively more rigid than in other peptides. Calcium-dependent swelling of liver mitochondria under the influence of four considered compounds was also investigated. Three of them were found to have the activity similar to cyclosporin A, inhibiting opening of the mitochondrial pore at concentrations within 100-300 nM. However, cyclosporin E did not show any biological effect at concentrations up to 1 µM. Results of this study agree with the idea on the correlation between the peptide chain flexibility and its bioavailability.

Polyurethane ionomers based on amino ethers of ortho-phosphoric acid.

The etherification of ortho-phosphoric acid with triethanolamine and polyoxypropylene glycol is studied. The reaction process is accompanied by the formation of hyperbranched amino ethers of ortho-phosphoric acid terminated by hydroxyl groups. A specific feature of the chemical structure of the compounds obtained is the existence of ion pairs in their structure separated in space. The reaction of the etherification of ortho-phosphoric acid with glycols becomes possible through the use of tertiary amines. The amino ethers of ortho-phosphoric acid are investigated as a polyol component for the synthesis of polyurethanes with high adhesion characteristics and strength properties. The experimental results presented allow us to relate polyurethanes obtained on the basis of ortho-phosphoric acid amino ethers to polymers of ionomeric nature.

Evidence of oligomerization of bovine insulin in solution given by NMR.

The protein hormone insulin exists in several forms in nature, and a large number of modified sequences are used in pharmacy. They differ by physicochemical properties and efficiency of biological action. Pancreatic bovine insulin was studied in an acidic solution by nuclear magnetic resonance spectroscopy. [Formula: see text]H and [Formula: see text]C NMR signal assignment of backbone and side chains was made by analysis of a set of 2D spectra obtained on a sample with natural isotope abundance. The presence of certain secondary structure elements was revealed on a qualitative level based on nuclear Overhauser effect spectroscopy, which are similar to those observed in the crystal structure. The C-terminus of the B-chain possessed a remarkable flexibility. The molecule was shown to exist in exchange with oligomers based on its self-diffusion coefficient and correlation time measurements performed at different concentrations. Certain signals in the NOESY and HSQC spectra are consistent with the presence of minor conformers; this is an obstacle in simulating the molecular structure under the conditions used in the experiment.

Antimicrobial peptide protegrin-3 adopt an antiparallel dimer in the presence of DPC micelles: a high-resolution NMR study.

A tendency to dimerize in the presence of lipids was found for the protegrin. The dimer formation by the protegrin-1 (PG-1) is the first step for further oligomeric membrane pore formation. Generally there are two distinct model of PG-1 dimerization in either a parallel or antiparallel ß-sheet. But despite the wealth of data available today, protegrin dimer structure and pore formation is still not completely understood. In order to investigate a more detailed dimerization process of PG-1 and if it will be the same for another type of protegrins, in this work we used a high-resolution NMR spectroscopy for structure determination of protegrin-3 (RGGGL-CYCRR-RFCVC-VGR) in the presence of perdeuterated DPC micelles and demonstrate that PG-3 forms an antiparallel NCCN dimer with a possible association of these dimers. This structural study complements previously published solution, solid state and computational studies of PG-1 in various environments and validate the potential of mean force simulations of PG-1 dimers and association of dimers to form octameric or decameric ß-barrels.

High-resolution NMR structure of the antimicrobial peptide protegrin-2 in the presence of DPC micelles.

PG-1 adopts a dimeric structure in dodecylphosphocholine (DPC) micelles, and a channel is formed by the association of several dimers but the molecular mechanisms of the membrane damage by non-α-helical peptides are still unknown. The formation of the PG-1 dimer is important for pore formation in the lipid bilayer, since the dimer can be regarded as the primary unit for assembly into the ordered aggregates. It was supposed that only 12 residues (RGGRL-CYCRR-RFCVC-V) are needed to endow protegrin molecules with strong antibacterial activity and that at least four additional residues are needed to add potent antifungal properties. Thus, the 16-residue protegrin (PG-2) represents the minimal structure needed for broad-spectrum antimicrobial activity encompassing bacteria and fungi. As the peptide conformation and peptide-to-membrane binding properties are very sensitive to single amino acid substitutions, the solution structure of PG-2 in solution and in a membrane mimicking environment are crucial. In order to find evidence if the oligomerization state of PG-1 in a lipid environment will be the same or not for another protegrins, we investigate in the present work the PG-2 NMR solution structure in the presence of perdeuterated DPC micelles. The NMR study reported in the present work indicates that PG-2 form a well-defined structure (PDB: 2MUH) composed of a two-stranded antiparallel ß-sheet when it binds to DPC micelles.

Determination of preferred conformations of ibuprofen in chloroform by 2D NOE spectroscopy.

Solution of an anti-inflammatory drug ibuprofen ((RS)-2-(4-isobutylphenyl) propionic acid) in chloroform was studied by nuclear magnetic resonance spectroscopy. A set of 2D NOESY spectra was analyzed in order to obtain atom-atom distances. Since ibuprofen is known to exist as an ensemble of different conformations, these distances are averaged over the ensemble. To compare experimental and calculated distances, three models of averaging were concerned. Our data allowed to determine the dominant conformers of ibuprofen dissolved in chloroform. The population of conformers in the saturated solution leads to a certain crystal morphology formed within the nucleation process. Observed and calculated (13)C chemical shifts (at the DFT/B3LYP/6-311+G(2d,p) level) were in good agreement.

[Unusual alternations of floral organs in Paeonia: structure and possible mechanism of formation].

Morphological analysis of flowers was carried out in Paeonia cultivars. Some unusual alternations of floral organs were described: sepal-(petal-stamen) x N-carpel, where 2 < or = n < or = 4 (appearance of an additional zone of petal and stamen formation in the medial flower part). The identity of floral organs was not affected in the flowers with this unusual alternation. It was shown on the basis of mathematical simulation of the genes responsible for flower development that these alternations may be determined by increased pool of stem cells, which may lead to delayed termination of flower development.

[The characteristics of the corticosteroid receptors in the hormonal modification of the stress reactivity of rats]. / Kharakteristika kortikosteroidnykh retseptorov pri gormonal'noi modifikatsii stress-reaktivnosti u krys.

After neonatal administration of hydrocortisone the rat litter preserve inhibition of function of the hypophyseal-adrenal system at the age under 2 months. During the inhibition period, the number of corticosteroid receptors was decreased in the hypothalamus and hippocampus and increased in the hypophysis. At the 3-month age, binding of corticosteroids in these structures is restored.

[The evaluation of corticosteroid hormone receptor status in the brain structures of stressed and adrenalectomized rats]. / Otsenka sostoianiia retseptorov kortikosteroidnykh gormonov v strukturakh mozga stressirovannykh i adrenaléktomirovannykh krys.

The value of receptor capacity in respect to cytosol concentration was shown to vary, therefore two criteria are proposed for estimation of condition of the cytosol corticosteroid receptors: the density of the receptors in tissue and the range of intermediate (active) complex. The number of receptors in the hypophysis was shown to reduce after adrenalectomy whereas in the hypothalamus, hippocampus and striatum it increased. The range of intermediate complex was shown to change differently in different structures after stress.

[The properties of the glucocorticoid receptors in the striatum and hypothalamus of rats selected for the threshold of excitability of their nervous systems]. / Svoistva gliukokortikoidnykh retseptorov v striatume i gipotalamuse krys, selektirovannykh po porogu vozbudimosti nervnoi sistemy.

In rats selected by their threshold sensitivity to electrical current, linear differences were found both at the receptor level and in stress-reactivity, the receptor lability being very high in the rats highly sensitive to electricity. The lower sensitivity rats were found to be more conservative in these parameters. The role of the hypothalamus and striatum in regulation of the hypophyseal-adrenocortical system through a feed-back mechanism, is discussed.

[The kinetic characteristics and stoichiometry of corticosterone interaction with cytosol receptors]. / Kinetichskaia kharakteristika i stekhiometriia vzaimodeistviia kortikosterona s tsitozol'nymi retseptorami.

The interaction of molybdate-stabilised cytosol receptor of the rat brain and liver with corticosterone was studied in conditions of equilibrium and non-equilibrium in vitro. The hormone-receptors complexes with varying number of the receptor molecules were found to form consequentially. During their formation the complexes revealed the properties of disperse phases. The concentration of the receptors seems to be one of the regulating factors of activity of the complexes. An original experimental technique is described.

[The dynamics of the microbiocenosis in the burrows of the little suslik]. / Dinamika mikrobiotsenoz nor malogo suslika.

Microbiocoenoses being formed in burrows of little souslik have been investigated. Microbiocoenoses of sloping burrows have most simple organization. Comparative analysis of the fauna and functional structure, conducted during the spring-summer period, has not shown the existence of any directed process in the development of microbiocoenoses of sloping burrows. On the contrary, microbiocoenoses of vertical nest burrows can be regarded as biocoenotic systems dynamic in space and time. Here in the period of rodent's vital activity occurs a constant construction of underground passages and periodical change of nests. In this case the fauna of new nests is formed largely at the expense of migration of nidicols along free or obstructed with loose earth underground horizontal passages. Microbiocoenoses in burrows of different types are not connected between each other by morphoprocess and their development is of independent character.

[An optical sensor for analyzing the flow of biological particles in chromatographic processes]. / Opticheskii datchik dlia analiza potoka biologicheskikh chastits v protsessakh khromatografii.

The design of an optic flow sensor operating in the UV spectrum is described. The sensor is intended to monitor changes in the size and/or concentration of light-diffusing particles against the background of low-molecular admixtures, as well as for analysis of these admixtures. The sensor has been employed in gel chromatography and adsorption chromatography of virus-containing suspensions.