From Peptides to Receptors

In the 1960s and 1970s, the Institute of Chemistry of Natural Compounds developed a topochemical approach for designing new biologically active peptide compounds, the applicability of which to the creation of inhibitors and effective substrates of proteolytic enzymes was shown by the author of this review under the direct supervision of V.T. Ivanov. The next task was to establish the conformation of protein neurotoxins from snake venoms and to study the topography of their binding to the target, the nicotinic acetylcholine receptor (nAChR) from the electric organ of the Torpedo marmorata ray. With selectively labeled derivatives containing one fluorescent or spin label on established amino acid residues, neurotoxin residues in contact with nAChR were identified for the first time. Later, in collaboration with the laboratory of V.T. Ivanov, new analogues of α-conotoxins (peptide neurotoxins from poisonous mollusks Conus), were synthesized including their photoactivated derivatives, which showed the participation of all Torpedo nAChR subunits in the binding of α‑conotoxins. The final part of the review briefly presents the recent achievements of the Department of Molecular Neuroimmune Signaling (headed by V.I. Tsetlin) concerning the isolation and synthesis of new peptide and protein neurotoxins and the study of their mechanism of action.