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Biomedical subjects

A A Akhrem

Publications and source records attributed to A A Akhrem.

At least 145 records · Page 8Linked to original sources

[Spatial structure of the rp142 peptide containing the immunodominant epitope of the HIV-1 gp120 protein. A theoretical study].

A model of spatial structure of the synthetic peptide rp142 (24 amino acid residues) containing the immunodominant epitope of the HIV-1 protein gp120 in the region Gly-10-Phe-15 was constructed by the method of "constrained" molecular mechanics, which uses the algorithms of theoretical conformational analysis, based on NMR spectroscopy data. A comparative analysis of calculated conformations revealed that the spatial structure of rp142 in solution can be described by a family of conformations to which nine different structural clusters involving the sets of topologically close conformers correspond. It is shown that the main chain of the peptide forms irregular but "structured" conformations in which the main portion of amino acid residues is incorporated into beta-turns and helix-like fragments, while Pro-11 and Gly-12 form in some structures inverse gamma-turns, which rarely occur in protein-peptide molecules. It was found that the spatial packing of the Gly-10-Phe-15 hexapeptide in different clusters is realized at different internal rotation angles, to which topologically close structures correspond. It is assumed that this invariant structural element describes the "conformation of complex formation" that is complementary to the antigen-binding center of antibodies and is responsible for their binding to the peptide.

Amino Acid Sequence↗

[Nucleoprotein melting. I. Theory of helix-coil transition of DNA in the presence of proteins with cooperative character of interaction under conditions of reversible binding].

Helix-coil transition of DNA with attached extended ligands able to interact with one another during adsorption on DNA (cooperative or uncooperative binding) has been considered. The general formulae describing dependence of polymer melting curve on concentration of attached ligands have been obtained. It has been shown that cooperativity of interaction with DNA stipulates for two phase profile of the melting curve. The results obtained show that proteins which interact with DNA cooperatively may cause two phase helix-coil transition under conditions of reversible binding.

DNA↗

[Effect of Ca2+ ions on thermal denaturation of chromatin in an aqueous medium].

Thermal denaturation of chromatin has been investigated in the presence of Ca2+ ions by adiabatic scanning microcalorimetryc and thermomechanical methods. In contrast to EDTA treated chromatin with two melting bands (74 degrees C and 82,5 degrees C) on differential melting curve, the only denaturation peak (82 degrees C) was observed in the presence of a very low Ca2+ level (0,1 mM). Chromatin melting temperature has been shown to decrease with Ca2+ concentration and in the region of 65-67 degrees C a heatless transition due to chromatin repacking in a more compact form occurred.

Calcium↗

[Local structure of cytochrome c from horse heart in solution. Conformational analysis using data of two-dimensional nuclear Overhauser effect spectroscopy].

Using the earlier suggested method the calculation of the backbone conformations of horse heart cytochrome c in oxidized (ferricytochrome c) and reduced (ferrocytochrome c) states has been performed by the two-dimensional nuclear Overhauser effect spectroscopy data. For both protein forms the secondary structure elements have been revealed and the conformations of the irregular polypeptide chain segments have been analysed. The similarity of the secondary structures of ferri- and ferrocytochrome c in solution was established from the comparison of their conformations. Small differences between the conformations of two molecule forms are shown to be localized within the polypeptide chain fragments situated in the spatial structure near the heme crevice. The comparison of the dihedral phi and psi angles in the calculated conformations of horse cytochrome C with the corresponding characteristics of X-ray structures of tuna ferri- and ferrocytochrome c made for the oxidized and reduced protein forms using the quantitative criteria testifies the similarity of their conformations in solution and crystal. In is shown that the conformational changes of the separate amino acid residues which take place as the result of the "solution-to-crystal" transition occur on the surface fragments of protein globule and do not lead to essential alterations of the secondary molecule structure.

Amino Acids↗

[Spatial structure of apamin in solution].

The calculation of the complete spatial structure of the bee venom peptide neurotoxin apamin has been carried out by means of a method elaborated earlier. It is based on the joint utilization of the molecular mechanics algorithms and NMR spectroscopy data. It was established that the molecule backbone conformation in solution may be represented as the combination of the beta-turn III (residues 2-5) and alpha-helical segment (9-18) both separated by the non-standard bend IV (5-8). The most probable system of the intramolecular hydrogen bonds in the apamin polypeptide backbone was proposed. Certain amino acid residues have been shown to be characterized by the lack of strict determination of the conformations of their side chains which may be realized in a few states providing approximately equal stabilization of the same form of the main chain. The conformational parameters of the proposed apamin structural model are appropriate to the NMR spectroscopy data derived from the literature and used in the calculations and are not contradictory to other experimental information.

Amino Acid Sequence↗

[New possibilities in searching for immunomodulators among compounds with a steroid structure].

It was shown that a phytosteroid ecdisterone which is the principle of a new tonic drug ecdisten in doses of 5-20 mg/kg is able to stimulate the primary immune reaction slightly effecting the indices of T-cell immunity activity and phagocyte functions. On increasing ecdisterone dose to 50 mg/kg inhibition of the number of antibody cells in the mouse spleen was marked.

Adjuvants, Immunologic↗

[The effect of long-range interactions between adsorbed ligands on the DNA helix-coil transition].

The influence of different types of long-range interaction of ligands adsorbed on DNA on the helix-coil transition was theoretically considered. The contact interaction was shown to differ significantly from the long-rang one. It was shown also that even weak dependence of a long-range potential on a degree of helicity resulted in the strong changes of a DNA melting curve. This result allowed to understand the different experimental data on DNA melting in the presence of different substances which reduced AT-and GC-base pairs thermostability difference.

Adsorption↗

[DNA helix-coil transition in alkaline medium].

Dna helix-coil transition in th alkaline medium was considered theoretically and experimentally. On the basis of the theory and experimental comparison the DNA double-stranded form deprotonation was revealed.

Alkalies↗

[The use of hemoglobin for determination of phospholipase A2 activity].

A spectrophotometric method is proposed for determining phospholipase A2 activity, which is based on the conversion of hemoglobin into hemichrome under the fatty acid action. The spectral difference between hemoglobin and hemichrome was registered by the difference spectrum with a minimum at 405 nm and a maximum at 423 nm. The absorption value determined as the difference between the spectrum maximum and minimum was proportional to the amount of the fatty acid derived from hydrolysis of phospholipids. The method enables the enzyme activity to be determined directly in the spectrophotometric cell.

Hemoglobins↗

[Temperature quenching of cytochrome P-450 fluorescence in proteoliposomes with different physical states of the lipid bilayer].

Studies were carried out of temperature quenching of self-fluorescence of cytochrome P-450 in solution and liposomes from natural phosphatidylcholine, dimiristoylphosphatidylcholine, dipalmitoylphosphatidylcholine. The fluorescence spectrum of cytochrome P-450 is a superposition of triptophane and tyrosine components. During protein incorporation into liposomes a significant short-wave shift of the emission spectrum takes place. Temperature dependence of the intensity of cytochrome P-450 self-fluorescence in solution has bends at 30, 45 and 50 degrees C. When protein is incorporated into liposomes the location of bends depends on individual properties of lipids forming the bilayer. Effect of lipid surrounding on temperature conformational rearrangements of cytochrome P-450 molecule is discussed.

Cytochrome P-450 Enzyme System↗

[Prognosis of the degree of exposure of amino acid residues in globular proteins in relation to various problems of protein engineering].

The algorithm was developed to predict the degree of exposure of amino acid residues in globular proteins. This algorithm combined with standard discriminant analysis methods was used for evaluation of the accessibility of Lys and Arg residues for trypsin-like proteases attack. The procedure can be useful for a computer-aided design of prolonged-action protein drug preparations.

Amino Acids↗

[Thermal denaturation of DNA in concentrated salt-free solutions: comparison of microcalorimetric and spectrophotometric data].

Scanning microcalorimetry and spectrophotometry were used to study the dependence of melting enthalpy (delta Hm) and temperature (Tm) on DNA concentration in salt free solutions and on NaCl concentration in solutions with constant DNA concentration. This data is used to calculate the Manning's charge density parameter which is found to be equal 1.8. The linear dependence of Tm on the logarithm of DNA concentration in salt free solution was obtained. An approximate evaluation of dissociation degree in native DNA at different concentrations was made by comparison of straight lines in the Tm = f(lg CNaCl) and Tm = f(lg Cp) coordinates.

Animals↗

[Influence of ligands characteristic of selective binding to a certain type of base pairs on DNA helix-coil transition I. Model. Theory].

The DNA helix-coil transition in the presence of ligands interacting selectively with a certain type or types of base pairs has been considered. A calculation method for estimation the influence of lignads on the melting process for which the knowledge of DNA primary structure is not required was proposed. It has been shown that the reverse temperature shift caused by ligands bound to a given type of base pairs at given kind of regions (helix or coli) is in direct proportion to the fist derivative with respect to the degree of helicity from ratio beta ji/n, where beta ji--number of nitrogen bases of i-type at the regions of j-kind; N--total number of DNA base pairs. It was assumed earlier that this shift was in direct proportion to beta ji/Nj, where Nj--number of base pairs in DNA regions of j-kind. The specificity of lignads interaction with given kinds of bases alters the manner of the melting process of the heteropolynucleotide in comparison with homopolynucleotide only in the case when the DNA primary structure has a strong influence on the position of helix and coli regions along the DNA chain. Only when this conditions is fulfilled the inversion of thermostability of AT- and GC-pairs may affect the shape of the melting curve.

Base Composition↗