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Muscarinic Toxin 3  

Muscarinic acetylcholine receptor(M₄) specific ligand

Muscarinic acetylcholine receptors have been classified into five subtypes (M₁ – M₅). These receptors are involved in various biological functions, which can be studied using specific ligands to each receptor subtype, including the peptidic “muscarinic toxins” (abbreviated as MT in this short description). Muscarinic toxins are isolated from the venom of the mamba species and are composed of 65 to 66 amino acid residues with four intramolecular disulfide linkages[Life Sci., 68, 2541 (2001), Pharmacol. Ther., 85, 87 (2000) ]. Recent work has indicated that the activation of muscarinic acetylcholine receptors can regulate the metabolism of β-amyloid precursor protein, and that muscarinic agonists led to a reduction of amyloid β-protein production[Brain Res., 905, 220 (2001), J. Protein Folding Disord., 10, 1 (2003)]. Synthetic Muscarinic Toxin 7 has been used to study M₁ receptor’s role in amyloid β-protein-induced signaling[J. Biol. Chem., 278, 17546 (2003)]. We have now successfully synthesized two additional muscarinic toxins bearing different receptor subtype selectivity.

Muscarinic Toxin 3 (MT3):

    Leu-Thr-Cys-Val-Thr-Lys-Asn-Thr-Ile-Phe-Gly-Ile-Thr-Thr-Glu-Asn-Cys-Pro-Ala-Gly-
    Gln-Asn-Leu-Cys-Phe-Lys-Arg-Trp-His-Tyr-Val-Ile-Pro-Arg-Tyr-Thr-Glu-Ile-Thr-Arg-
    Gly-Cys-Ala-Ala-Thr-Cys-Pro-Ile-Pro-Glu-Asn-Tyr-Asp-Ser-Ile-His-Cys-Cys-Lys-Thr-
    Asp-Lys-Cys-Asn-Glu

One of these is muscarinic toxin 3 (MT3) which was isolated from the green mamba (Dendroaspis augusticeps) and is composed of 65 amino acid residues. This peptide shows selectivity for the M₄ receptor with low affinity to M1 receptor[FEBS Lett., 352, 91 (1994)], and no binding to M2, M3, and M5 receptors[FEBS Lett., 352, 91 (1994), Toxicon, 34, 1257 (1996), Life Sci., 60, 1069 (1997), Eur. J. Pharmacol., 357, 235 (1998)].

Combined utilization of these chemically synthesized muscarinic toxins together with already commercially available MT1 and MT7, the research concerning biological functions elicited through muscarinic acetylcholine receptors should advance significantly.

Related Peptide

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