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Vol. 24, Art. 65 (pp. 921-972)    |    2023       

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Hapten-carrier conjugates with haptens-analogues of psychoactive substances and toxicants: algorithms for modeling the molecular structure of synthetic compounds haptene epitopes in designing of immunogenic antigens

Kozlov V.K.1,2*, Bespalov A.Ya.1, Кashuro V.А.2,3,4
1 Scientific and clinical center of toxicology named after academician S.N. Golikov
FMBA of Russia, 192019, St. Petersburg, st. Bekhtereva 1.;
2 St. Petersburg State University, St. Petersburg, Mendeleevskaya line 2;
3 St. Petersburg State Pediatric Medical University of the Ministry of Health of Russia,
194100, Russian Federation, St. Petersburg, st. Lithuanian 2;
4 Federal State Budgetary Educational Institution of Higher Education Russian State Pedagogical University. A.I. Herzen
191186, Russian Federation, St. Petersburg, emb. Moika River, 48.

Brief summary

Based on the analysis of the available literature data and the authors' own experience in the field of constructing hapten-carrier conjugates with haptens-analogues of low molecular weight chemical compounds (including psychoactive medicines, synthetic drugs, organophosphorus neurotoxicants), the ways and algorithms for creating immunodominant hapten epitopes in the composition of such immunogens are described. Algorithms for ensuring the target specificity of hapten epitopes in the composition of conjugated antigens (immunogens) used for the purposes of active immunization are summarized on specific examples of obtaining conjugated antigens with hapten analogues of psychoactive and neurotoxic chemical compounds: synthetic drugs (methamphetamine, phencyclidine); psychoactive tricyclic antidepressants and neuroleptics (for example, perphenazine, imipramine, chlorpromazine, trifluoperazine, fluphenazine and others); antidepressants of other pharmacological groups (for example, derivatives of 1,4-benzodiazepine); synthetic central anticholinergics with psychodysleptic (psychotomimetic) activity (trihexyphenidyl, benztropine, pirenzepine, glipin); cholinesterase inhibitors - organophosphorus compounds and aminostigmine. The most frequently used approaches for optimizing the methods for the synthesis of hapten analogs of these psychoactive or toxic compounds and the corresponding conjugated antigens are also summarized. It is postulated that the algorithm for such optimization is determined by the molecular structure of target chemical compound and the choice of a specific reactive (functional) group that is introduced into the hapten analog. For the purposes of obtaining haptens analogs of psychoactive medicines and drugs or toxic chemical compounds with a reactive carboxyl group, a universal optimization algorithm is the synthesis of their hemisuccinate derivatives. Using specific examples of hapten analogs with reactive carboxy and amino groups, methods for their conjugation to macromolecular, predominantly protein, carriers are described and generalized too.


Key words

psychoactive substances; synthetic drugs; organophosphate neurotoxicants; conjugated antigens (hapten-carrier conjugates); hapten analogues of synthetic psychoactive substances and organophosphorus neurotoxicants; hapten determinants (epitopes); immu

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