PubMed Health⌕ Search

Biomedical subjects

A A Akhrem

Publications and source records attributed to A A Akhrem.

At least 19 recordsLinked to original sources
PubMed1998

Melting of cross-linked DNA. III. Calculation of differential melting curves.

In our previous papers I and II (D. Y. Lando et al, J. Biomol. Struct. Dynam. (1997) v. 15, N1, p. 129-140, p. 141-150), two methods were developed for calculation of melting curves of cross-linked DNA. One of them is based on Poland's and another on the Fixman-Freire approach. In the present communication, III, a new theoretical method is developed for computation of differential melting curves of DNAs cross-linked by anticancer drugs and their inactive analogs. As Poland's approach, the method allows study of the influence of the loop entropy factor, delta(n), on melting behavior (n is the length of a loop in base pairs). However the method is much faster and requires computer time that inherent for the most rapid Fixman-Freire calculation approach. In contrast to the computation procedures described before in communications I and II, the method is suitable for computation of differential melting curves in the case of long DNA chains, arbitrary loop entropy factors of melted regions and arbitrary degree of cross-linking including very low values that occur in vivo after administration of antitumor drugs. The method is also appropriate for DNAs without cross-links. The results of calculation demonstrate that even very low degree of cross-linking alters the DNA differential melting curve. Cross-linking also markedly strengthens the influence of particular function delta(n) upon melting behavior.

Cross-Linking Reagents↗
PubMed1997

Melting of cross-linked DNA: II. Influence of interstrand linking on DNA stability.

In the previous paper (D.Y. Lando, J. Biomol. Struct. Dynam, 15, 129-140 (1997)) the melting of cross-linked DNA with N base pairs and omega interstrand cross-links has been considered theoretically. In the present study on the basis of these results, two simple schemes are developed for the computation of melting curves of cross-linked DNA. The investigation of influence of interstrand linking on DNA stability has been carried out by computer simulation. It is shown that the relative concentration of cross-links, CCT = omega/N, their distribution along a DNA molecule, and particular values of the entropy factors of small loops formed by cross-links in melted regions strongly affect the DNA melting temperature, Tm. On the contrary, for DNA without cross-links, a ten-fold increase or decrease in the entropy factors of small loops does not cause the Tm variation. The comparison of the results of calculation with experimental data suggests that the majority of types of cross-link neither maintain ordered parallel orientation of bases in melted regions nor increase considerably the thermostability of cross-linked base pairs. Four different ways of influence of interstrand cross-linking on the DNA double helix stability are considered. It is shown that cross-linking significantly enhances the influence of single strand stiffness in melted regions on DNA melting behavior.

Computer Simulation↗
PubMed1995

[Synthesis and properties of membrane-addressed antioxidants based on phosphorylated pyrocatechols].

Amphiphilic membrane-addressed antioxidants differing in their hydrophobic-hydrophilic balance, 3,5-di-tert-butyl-2-hydroxyphenyl phosphate, (3,5-di-tert-butyl-2-hydroxyphenyl)hexadecyl phosphate, and (3,5-di-tert-butyl-2-hydroxyphenyl)-5-cholesten-3 beta-yl phosphate, were synthesized starting from 3,5-di-tert-butyl-o-quinone. Even at 10(-8) M concentration, 3,5-di-tert-butyl-2-hydroxyphenyl phosphate and (3,5-di-tert-butyl-2-hydroxyphenyl)hexadecyl phosphate inhibit formation of malonic aldehyde during peroxidation of lipids from rat brain homogenate initiated with a Fe(2+)-ascorbate system. At 10(-4) M and higher concentrations of antioxidants in the brain homogenate, the formation of malonic aldehyde is inhibited more efficiently than with tocopherol at the same concentrations.

Animals↗
PubMed1994

Theoretical and experimental study of DNA helix-coil transition in acidic and alkaline medium.

The theoretical approach to the calculation of the influence of selective binding of small ligands on DNA helix-coil transition has been described in the previous paper (Lando D. Yu., J. Biomol. Struct. Dyn., (1994)). In the present paper that method is used for the study of DNA protonation and deprotonation in acidic and alkaline medium by theoretical analysis of pH effect on DNA heat denaturation. The mechanism of DNA protonation in acidic medium and pK values of nucleotides are well known. It gave us an opportunity to check the theory without any fitting of pK values. A good agreement between experimental and calculated functions Tm(pH) and delta T(pH) (melting temperature and melting range width) obtained for acidic medium proved the validity of the theory. However, for alkaline medium there was not even qualitative agreement when the agreed-upon mechanism of deprotonation was considered. Looking into the cause of the discrepancy, we have studied the DNA melting for different mechanisms of deprotonation by calculation of Tm(pH) and delta T(pH). As a result, it has been established that the discrepancy is due to deprotonation of bonded GC base pairs of helical DNA regions (pK = 11). It was shown that the early known protonation and newly found deprotonation of helical DNA essentially stabilised double helix in alkaline and acidic medium.

Animals↗
PubMed1992

[Lipolysis in model membranes in the presence of positively charged soluble proteins].

Phospholipase A2 hydrolysis of neutral and negatively charged lipid membranes modified by positively charged proteins has been studied using liposomes composed of either dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylglycerol (DOPG) alone or their equimolar mixture in the presence of cytochrome c, histone H1, cytochrome b5, and polylysine. Twenty minutes after the reaction had been initiated, DOPC hydrolysis was 58%, while that in the equimolar mixture with DOPG was 35%. DOPG hydrolysis was more complete in binary mixtures of liposomes. The same was observed for liposomes in the presence of cytochrome c. Hydrolysis of phospholipids in binary liposomes in the presence of histone H1 was 3 times faster than that in protein-free liposomes. In the presence of polylysine the rate of DOPG hydrolysis was decreased. The results obtained are suggestive of electrostatic interactions between hydrophilic proteins and negatively charged phospholipids, the phospholipase A2 catalytic activity being affected by these interactions.

Cytochrome c Group↗
PubMed1990

A method for determining the relative effect of ligands on A-T and G-C base pairs in DNA: applications to metal ions, protons and two amino acids.

A new method is described for the study of specific interactions of low-molecular ligands with the base pairs of DNA. This method is based on the comparative analysis of melting temperature changes in DNAs of different GC-content in the presence of low molecular weight ligands. In this paper, the method is applied to Mn2+, Ni2+, Co2+ ions, deprotonation, amino acids, beta-alanine and gamma-aminobutyric acid (gamma-ABA). Differences in Tm are affected not only by the changes of relative stability of AT- and GC-pairs, but also by other factors. A theoretical analysis of the sequence specificity of low-molecular ligands on the base pairs in DNA molecules characterized by a high degree of sequence heterogeneity is also presented.

Adenine↗
PubMed1990

[Regulation of the catalytic activity of the monooxygenase enzyme system depending of the substrate structure and phospholipid composition of the model membrane].

A comparative study of pentoxy- and benzyloxyresorufin dealkylation by a monooxygenase enzyme system in dilauroylphosphatidylcholine micelles and in proteoliposomes was carried out. In proteoliposomes whose lipid matrix is formed by double phospholipid mixtures, a cooperative regulation of the oxidation reaction was found. It was shown that the cooperativity of this process depends on the substrate type as well as on the phospholipid composition of the vesicles and decreases during peroxide oxidation of lipids. The results obtained are discussed in terms of protein-protein and protein-phospholipid interactions in the oligomer ensembles consisting of several cytochrome P-450 LM2 molecules.

Animals↗
PubMed1989

Hemoglobin conversion to hemichrome under the influence of fatty acids.

The effect of free fatty acids on the process of hemoglobin conversion and lipid peroxidation has been studied in model systems and erythrocytes. It has been found that methemoglobin and oxyhemoglobin are converted to the low spin oxidized form, namely, reversible hemichrome under the action of fatty acids. In the case of oxyhemoglobin, an increase in the level of active oxygen forms is observed in the system which initiates the formation of primary and secondary lipid peroxidation products. Incubation of erythrocytes with free fatty acids causes the formation of Heinz bodies and is accompanied by an increase of the lipid peroxidation level.

Arachidonic Acid↗
PubMed1989

Calcium tartrate gel.

A method for preparation of a gel for chromatography has been developed. The adsorbent is calcium tartrate treated with potassium phosphate. By changing the temperature of synthesis (10-65 degrees C) and concentration of the salts (calcium chloride and sodium potassium tartrate) from 0.3 to 3.0 M, we have been able to prepare adsorbent crystals of definite sizes in the range 35-200 microns. In all cases, for synthesis of adsorbent, the Ca2+/K+Na+ ratio was greater than 1. After treatment of calcium tartrate crystals with 0.075-1.5 M potassium phosphate at 80-100 degrees C and pH 8.5-9.0, an appropriate chromatographic adsorbent was prepared. The chromatographic properties of calcium tartrate gel have been studied. The adsorbent permits flow rates of 25-150 ml/h, depending on the particle size. The capacity of calcium tartrate gel for binding BSA, RNA, and DNA was similar to that of Tiselius' hydroxyapatite (A. Tiselius, S. Hjerten, O. Levin (1956) Arch. Biochem. Biophys. 65, 132-155). The spheric shape of gel particles permits uniform and compact packing of adsorbent under the conditions of column chromatography.

Calcium↗