Biomedical subjects

A I Luik

Publications and source records attributed to A I Luik.

11 recordsLinked to original sources

PubMed1998

Study of human serum albumin structure by dynamic light scattering: two types of reactions under different pH and interaction with physiologically active compounds.

The effect of pH and binding of ten physiologically active compounds (isoproterenol, yohimbine, propranolol, clonidine, phenylephrine, carbachol, tripeptide fMLP, diphenhydramine, chlorpromazine and atropine) on the molecular structure of human serum albumin (HSA) has been studied using the dynamic light scattering. It was found that albumin globule has the most compact configuration (Stokes diameter 59-62 A) at physiological pH 7.4. The changes in pH, both increase to 8.0 and decrease to 5.4, result in the growth of globule size to 72-81 A. At acidic shift of pH an additional peak arises in the correlation spectra caused by the light scattering on the structures with the Stokes diameters of 29-37 A. Those conform to the sizes of the albumin subdomains. The indicated peak is not displayed at basic shift of pH. The interaction with propranolol, clonidine, phenylephrine, carbachol and tripeptide fMLP which hinder adenylate cyclase (AdC) and activate Ca-polyphosphoinositide (Ca-PPI) signaling system of a cell initiates structural rearrangements similar to acidic transitions. Isoproterenol, yohimbine diphenhydramine, chlorpromazine and atropine, which activate AdC and hinder Ca-PPI, cause conformational changes of HSA similar to basic transitions.

Atropine↗

PubMed1998

The influence of pH alteration and pharmacological modulators of adenylate cyclase system on human serum albumin conformation.

The report describes the results of a study the effect of pH and binding of six physiologically active compounds (isoproterenol, yohimbine, theophylline, propranolol, clonidine and carbachol) on the molecular structure of human serum albumin (HSA) using dynamic light scattering. It was found that the albumin globule had the most compact configuration (Stokes diameter 59-62A) at physiological pH 7.4. The changes in pH both increased to 8.0 and decreased to 5.4, resulting in the growth of globule size to 72-81A. At acidic shift of pH an additional peak arose in the correlation spectra. This peak was caused by the light scattering on the structures with the Stokes diameters of 29-37A, which conformed to the sizes of the albumin subdomains. The additional peak was not displayed at basic shift of pH. The interaction with propranolol, clonidine and carbachol, which hinder adenylate cyclase (AdC) signaling system of a cell, initiated structural rearrangements similar to acidic transitions. Isoproterenol, yohimbine and theophylline, which activate AdC, caused the conformational changes of HSA similar to basic transitions.

Adenylyl Cyclases↗

PubMed1995

Effects of haloperidol and chlorpromazine on smooth muscle contractility, platelet aggregation and neuronal calcium current.

Effects of chlorpromazine, haloperidol (neuroleptics and calmodulin antagonists), and verapamil on rat platelet aggregation induced by thrombin, on calcium current in snail neurones and on both tonic tension of high potassium contracture and phasic contraction of isolated guinea-pig ureter preparations were studied. Moreover, droperidol, sulpiride and prazosine effects were studied for models of phasic contractility and platelet aggregation. Sulpiride and prazosine were ineffective, verapamil was ineffective on platelet aggregation, while droperidol was the most potent inhibitor of platelet aggregation. These results, the similarity revealed in the blockage of neuronal calcium current by neuroleptics and verapamil, and the potent inhibitory action of haloperidol and chlorpromazine on contractility and aggregation suggest that both phenothiazine and butyrophenone neuroleptics possess some properties of calcium antagonists and may also have intracellular sites of action other than calmodulin.

Animals↗

PubMed1994

HIV-1 reverse transcriptase inhibitor design using artificial neural networks.

Artificial neural networks were used to analyze and predict the human immunodeficiency virus type 1 reverse transcriptase inhibitors. The training and control sets included 44 molecules (most of them are well-known substances such as AZT, dde, etc.). The activities of the molecules were taken from literature. Topological indices were calculated and used as molecular parameters. The four most informative parameters were chosen and applied to predict activities of both new and control molecules. We used a network pruning algorithm and network ensembles to obtain the final classifier. Increasing of neural network generalization of the new data was observed, when using the aforementioned methods. The prognosis of new molecules revealed one molecule as possibly very active. It was confirmed by further biological tests.

Algorithms↗

PubMed1993

Applications of neural networks in structure-activity relationships of a small number of molecules.

We investigated the applications of back propagation artificial neural networks (ANN) for a small dataset analysis in the field of structure-activity relationships. The derivatives of carboquinone were used as an example. It's been found that in this case the use of the same neural network results in unambiguous classification of new molecules. Predictions can be improved with statistical analysis of independent prognosis sets. We suggest that the sign criterion be used as a classification rule. We also compared neural networks with FALS and ALS in leave-one-out prediction. ANN applied to the same dataset has shown the same predictive ability as ALS but poorer than FALS.

Carbazilquinone↗

PubMedDate not supplied

[Experimental analysis of embichin interaction with human serum albumin].

Study of embichin binding to human serum albumin in vitro by gel chromatography and fluorescence has shown that embichin is bound to human serum albumin with an association constant of 3.3 x 10(3) M-1. Interaction of embichin and albumin, that is reversible in the initial stages, transforms to irreversible on long-term contact of the protein with the drug. Experiments with cell culture indicate that the interaction with albumin potentiates the cytotoxic action of embichin.

Alkylation↗

PubMedDate not supplied

Ligand-receptor interactions. Multidimensional mathematical method of analysis.

The paper embraces information about the character of interaction between pharmacologically active ligands and 11 G-protein-dependent receptors of neurotransmitters. The data are analyzed by the methods of correlation and cluster analyses and of main components. An essential pharmacological affinity is revealed to exist between the receptors which regulate an inhibitory link of the adenylate cyclase system and receptors which activate Ca(2+)-mobilizing polyphosphoinositide system of secondary transmitters. Receptors which activate adenylate cyclase are rather different pharmacologically from two previous groups. Interrelation between the structure and physico-chemical properties of binding sites on receptors and efficiency of their interaction with ligand is discussed.

Adenylyl Cyclases↗

PubMedDate not supplied

Similarity of the effects of tosyl-L-arginine methyl ester, atropine, caffeine and antitumour alkylating agent on some biological functions of thrombin and platelet 12-lipoxygenase.

The effect of the synthetic thrombin substrate (TAME) and three compounds exerting an opposite effect on Ca-PPI and AdC (caffeine, atropine and meta-tolyl derivative of mechlorethamine (TDM)) on hormone-like and catalytic functions of thrombin was studied. It is shown that both TAME and other drugs under test block effectively the thrombin-induced platelet aggregation, as well as protect the active site of the enzyme from denaturation by dithiothreitol. The same compounds inhibit thrombin in thrombin-fibrinogen reaction and platelet 12-lipoxygenase. These data suggest identity of thrombin moieties which determine its enzymatic and hormone-like activities.

Alkylating Agents↗

PubMedDate not supplied

Mechanism of inhibiting effect of biologically active compounds on the active forms of oxygen reduction.

The impulse voltammetry methods with recording short-living radical-natured products of the reduction (in particular, hydroxyl radicals) are used to study the process of oxygen reduction steps. A possibility to study mechanisms of antioxidative action of biologically active compounds (BAC) through studying their influence on the separate steps of oxygen reduction (initial molecular oxygen, radical particles and peroxides) is shown. It provides a possibility for the purposeful search of BAC capable to affect certain steps of chain oxidation in biosystems.

Electrochemistry↗

PubMedDate not supplied

Physico-chemical similarity of neurotransmitter receptor and transporter transmembrane domains.

Receptor and transporter of neurotransmitters similarity in ability of ligand-binding makes us consider them to possess the sites of similar structure and physico-chemical characteristics. However direct analysis of amino acid sequences alignment did not allow revealing such sites. For functionally similar proteins that differ in primary structure, the similarity extent is satisfactory estimated as based on physico-chemical properties of individual domain. We have analyzed transmembrane domains of a set of receptors and transporters of choline, norepinephrine, dopamine and serotonin. In our analysis in direction from extracellular border to intracellular one, amino acid sequences of transmembrane domains were divided into fragments each consisting of 4 amino acids. Every fragment was characterized by physico-chemical properties, such as hydrophilicity, hydrophobicity, polarity, etc. Hierarchical cluster analysis in space of the physico-chemical properties of these fragments was performed. As a result we have obtained both heterogeneous clusters, which contained receptor and transporter fragments, and homogeneous clusters which contained only receptor or transporter domains. An analysis of heterogeneous clusters has shown that the 4th, 5th and 6th transmembrane receptor domains and the 2d, 3d and 7th transmembrane transporter helices possess maximum similarity. The results obtained allow one to make a conclusion that these domains take part in formation of the ligand-binding centers.

Animals↗

PubMedDate not supplied

Character of structural disturbances caused by chloroalkylamines in the model and erythrocyte membranes.

beta, beta-Dichlorodiethylamine is proved not to induce structural disturbances in phosphatidylcholine liposomes and erythrocyte membranes which is registered by fluorescence methods. Methyl-beta, beta-dichlorodiethylamine and metaxylyl-beta, beta-dichlorodiethylamine cause the increase in microviscosity of lipid bilayer hydrophobic areas in both erythrocyte membranes and liposomes. Besides, polarity of the latter also decreases, and the metaxylyl derivative alkylates nucleophilic centers of phospholipid phosphate groups in liposomes. Erythrocyte membranes, being treated by beta, beta-dichlorodiethylamine derivatives, the increase in the membrane protein hydrophobicity is registered as well as the decrease in their immersion in the lipid bilayer.

Antineoplastic Agents, Alkylating↗