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Vol. 24, Art. 64 (pp. 870-920)    |    2023       

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Hapten-carrier conjugates with haptens-analogues of psychoactive substances and toxicants: algorithms for modeling the molecular structure of alkaloid 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 conjugated antigens with hapten analogues of psychoactive and neurotoxic alkaloids, the principles of giving hapten epitopes the property of immunodominance in the composition of antigens (immunogens) and approaches (algorithms) for modeling the molecular structure of hapten epitopes that determine their specificity 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 alkaloids: morphine alkaloids - opiates; tropane alkaloids - cocaine, atropine, scopolamine, hyoscyamine; tropolone alkaloid - colchicine; proaporphine alkaloid - stefarin and some other alkaloids (for example, tobacco alkaloid - nicotine and alkaloid of snowdrop bulbs - galanthamine). Using examples of the synthesis of hapten analogs of psychoactive and neurotoxic alkaloids: morphine and tropane alkaloids, tobacco alkaloids, which are widely used for non-medical purposes as drugs (opiates, cocaine, psychodysleptic alkaloids, nicotine), the most commonly used approaches to optimizing synthesis methods are summarized too. It is postulated that the algorithm for such optimization is determined by the molecular structure of the target ligand and the choice of a specific reactive (functional) group that is introduced into the hapten analog. The methods of hapten analogs synthesis are very diverse. For the purposes of obtaining haptens analogs of psychoactive and toxic alkaloids 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. Thus, the most widely used methods of chemical conjugation make it possible to obtain immunogens with optimal molecular and immunochemical characteristics for inducing an intense and specific humoral immune response to the hapten epitope.


Key words

psychoactive and neurotoxic alkaloids; narcotic substances; conjugated antigens (hapten-carrier conjugates); haptens analogs of alkaloids; hapten determinants (epitopes); immunochemical specificity; modeling of biological activity and specificity.

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