Publications by authors named "Tatiana Syrejshchikova"

2 Publications

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Influence of Antipsychotic Drug Risperidone on Human Serum Albumin Affinity to Organic Anions.

Curr Drug Discov Technol 2018 ;15(3):263-269

Moscow Research Institute of Psychiatry, Moscow, Russian Federation.

Background: Risperidone is an antipsychotic drug. In blood, this drug binds mainly to human serum albumin (HSA) and is also transported by HSA.

Method: To study certain details of the interaction between risperidone and HSA, a fluorescent dye CAPIDAN was used as a reporter. This dye specifically fluoresces from HSA in serum and is highly sensitive to structural changes in HSA including pathology-induced changes. Interaction of CAPIDAN with HSA has been studied using time-resolved fluorescence techniques.

Result: The addition of phenylbutazone, a marker for the HSA drug-binding site I, leads to displacement of CAPIDAN from this site due to direct competition between phenylbutazone and the dye. The addition of risperidone induces a response of CAPIDAN fluorescence that is highly similar to its response to phenylbutazone. This response depends strongly on ionic strength and is very similar in both cases, phenylbutazone and risperidone. This similarity suggests that risperidone binds to HSA in the region of site I. In this site, the risperidone molecule probably covers the positive charge of Arginine 218 or Arginine 222 preventing their interaction with the CAPIDAN negatively charged carboxyl group. This effect was observed both in isolated HSA and in serum, suggesting similarity of the interaction.

Conclusion: Thus, risperidone is able to prevent binding of organic anions (i.e. CAPIDAN as a drug-like molecule) to HSA.
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August 2019

A fluorescent reporter detects details of aromatic ligand interference in drug-binding sites of human serum albumin.

Biochem Biophys Res Commun 2016 09 16;478(1):462-466. Epub 2016 Jun 16.

Moscow Research Institute of Psychiatry, 3 Poteshnaya, Moscow, 107076, Russia.

Human serum albumin (HSA) transports many ligands including small aromatic molecules: metabolites, drugs etc. Phenylbutazone is an anti-inflammatory drug, which binds to the drug-binding site I of HSA. Its interaction with this site has been studied using a fluorescent dye, CAPIDAN, whose fluorescence in serum originates from HSA and is sensitive to the changes in HSA site I in some diseases. Its fluorescence in HSA solutions is strongly suppressed by phenylbutazone. This phenomenon seems to be a basic sign of a simple drug-dye competition. However, a more detailed study of the time-resolved fluorescence decay of CAPIDAN has shown that phenylbutazone lowers fluorescence without changing the total amount of bound dye. In brief, the HSA-bound dye forms three populations due to three types of environment at the binding sites. The first two populations probably have a rather strong Coulomb interaction with the positive charge of residues Arginine 218 or Arginine 222 in site I and are responsible for approximately 90% of the total fluorescence. Phenylbutazone blocks this interaction and therefore lowers this fluorescence. At the same time the binding of the third population increases considerably in the presence of phenylbutazone, and, as a result, the actual number of bound dye molecules remains almost unchanged despite the ligand competition. So, time resolved fluorescence of the reporter allows to observe details of interactions and interference of aromatic ligands in drug binding site I of HSA both in isolated HSA and in serum.
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September 2016