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Biomedical subjects

A E Gabriélian

Publications and source records attributed to A E Gabriélian.

8 recordsLinked to original sources

[Modeling antigenic determinants of the hepatitis A virus using synthetic peptides].

Monoclonal and polyclonal anti-hepatitis A (HAV) antibodies were used to search for peptides mimicking the antigenic determinants of HAV. Synthetic peptides VP1 115-139, VP1 117-139, VP1 126-139, VP2 69-99, VP2 80-99, VP3 45-57, VP3 137-150, were shown to bind the anti-HAV antibodies in ELISA. Peptides VP1 115-139, VP1 117-139, VP2 69-99 were utilized to produce the antipeptide antibodies. Mice were immunized with the free peptides or with their conjugates with ovalbumin. Only the free VP2 69-99 caused formation of HAV binding antibodies.

Amino Acid Sequence↗

[Search for T-epitopes of the hepatitis A virus using synthetic peptides].

Computer search for probable T-epitopes of the hepatitis A virus capsid proteins was performed using developed integrated set of programmes. The following peptides were chosen and synthesised by solid phase technique: 75-92 VP1, 115-139 VP1, 209-221 VP1, 69-99 VP2, 80-99 VP2, 45-57 VP3, 137-150 VP3 and 1-23 VP4. Peptides 1-17 VP1, 10-33 VP1, 11-25 VP1, 75-85 VP1 and 276-298 VP1 previously examined as probable B-epitopes were used as well. All the peptides were tested for their ability to stimulate proliferation of lymph node T-cells primed with synthetic peptides. Almost all the predicted T-epitopes did affected the T-cell proliferation. 10-33 VP1 and 276-298 VP1 stimulated lymph node proliferation of all tested mouse strains. 107-126 VP1 and 115-126 VP1 did not influence proliferation of lymphocytes of mice primed with these peptides but stimulated proliferation of T-cells of F1 (CBA x C57Bl6) mice primed with 115-139 VP1.

Animals↗

[A method of searching for amphipathic structures in protein sequences].

A simple method for searching amphipathic helices based on estimation of correlation between hydrophobicity distribution and periodic function is proposed. The method was examined in a series of proteins with known T-cell epitopes, which are mostly amphipathic helices. The predictive power of the method is discussed.

Algorithms↗

[Theoretical analysis of the amino acid sequence of receptors for growth hormones and prolactins. Prediction of ligand-binding segments].

At present the growth hormone and prolactin receptors were cloned along with their variant forms from human, rat, mouse, rabbit, bovine and sheep tissues. The functional topography of receptors is practically unknown. Because of the high price and difficulty of protein's total mutagenesis, it is reasonable to carry on a theoretical analysis of structures of receptors to predict the most probable ligand-binding sites. We studied the primary structures of known prolactin and growth hormone receptors using theoretical methods proved to be powerful in earlier structure--activity relationship investigations. We analyzed the secondary structure, conservative positions, hydrophilicity profiles of the growth hormone and prolactin receptors, and used the original method based on information theory to predict the sites which are promising for mutagenesis or peptide synthesis as probable ligand-binding sites. Three segments corresponding to the main conservative, hydrophilic and rare sites were predicted to form the ligand-binding determinant.

Amino Acid Sequence↗

[Use of frequency analysis for localization of functionally important regions of thermolysin].

A theoretical investigation of the functional topography of thermolysin molecule was carried out using frequency analysis of its primary and tertiary structures. The statistical validity of predictions was estimated for the enzyme active site, substrate-binding pocket, interdomain interface, and calcium-binding sites. It was shown that frequency analysis of primary structure could be employed to predict the localization of contiguous parts of the interdomain interface. Primary structure analysis cannot be used to search for the conformation-dependent enzyme active site and substrate-binding pocket. On the contrary, frequency analysis of interresidues contacts is not so effective for prediction of the interdomain interface as compared with active site, substrate-binding pocket, and calcium-binding sites. The set of original algorithms proposed could be used in searching for functional sites in various proteins.

Amino Acid Sequence↗

[Artificial proteins with a given spatial structure and biological activity].

Biologically active fragment 131-138 of human interferon alpha 2 carrying blast-transforming activity of the protein was attached to the N-terminus of the de novo protein albebetin with predetermined tertiary structure by means of genetic engineering. The chimeric protein was expressed in a wheat germ cell-free translation system and tested for compactness, stability and biological activity. According to the tests used albebetin with interferon fragment has a compact and relatively stable structure. It binds murine thymocyte receptor with high affinity and activates efficiently thymocyte blast transformation at a concentration of 10(-11) M.

Amino Acid Sequence↗