Two new classes of conopeptides inhibit the α1-adrenoceptor and noradrenaline transporter

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Abstract
Cone snails use venom containing a cocktail of peptides ('conopeptides') to capture their prey. Many of these peptides also target mammalian receptors, often with exquisite selectivity. Here we report the discovery of two new classes of conopeptides. One class targets α1-adrenoceptors (ρ-TIA from the fish-hunting Conus tulipa), and the second class targets the neuronal noradrenaline transporter (χ-MrIA and χ-MrIB from the mollusk-hunting C. marmoreus). ρ-TIA and χ-MrIA selectively modulate these important membrane-bound proteins. Both peptides act as reversible non-competitive inhibitors and provide alternative avenues for the identification of inhibitor drugs.