Abstract
An efficient scheme for the synthesis of α-conotoxins, containing 12–18 amino acid residues and two disulfide bridges, was proposed. Its advantages are: (1) the avoidance of orthogonal protections of Cys residues; (2) a lower number of stages in a cycle of the peptide chain elongation by the method of solid phase synthesis; (3) the linear product is sufficiently pure for being used at the next stage of the disulfide bond formation without additional purification; and (4) a substantially reduced time of oxidation to disulfides at pH 10, which led to the target product in a high yield. A number of natural α-conotoxins (GI, ImI, EI, MII, and SIA), affecting the muscle and neuronal nicotinic acetylcholine receptors of various types, and several new analogues of these conotoxins (in particular, [Tyr10]ImI, [Gln12]GI, and [Ser1]GI) were synthesized by this scheme. They were used for elucidating the spatial structure of α-conotoxins by 1H NMR spectroscopy and for studying the ligand-binding sites of their receptors.
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Zhmak, M.N., Kasheverov, I.E., Utkin, Y.N. et al. An Efficient Synthetic Scheme for Natural α-Conotoxins and Their Analogues. Russian Journal of Bioorganic Chemistry 27, 67–71 (2001). https://doi.org/10.1023/A:1011319101676
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DOI: https://doi.org/10.1023/A:1011319101676