Structure‐activity relationships of α‐conotoxins targeting neuronal nicotinic acetylcholine receptors

α‐Conotoxins that target the neuronal nicotinic acetylcholine receptor have a range of potential therapeutic applications and are valuable probes for examining receptor subtype selectivity. The three‐dimensional structures of about half of the known neuronal specific α‐conotoxins have now been determined and have a consensus fold containing a helical region braced by two conserved disulfide bonds. These disulfide bonds define the two‐loop framework characteristic for α‐conotoxins, CCX m CX n C, where loop 1 comprises four residues (m = 4) and loop 2 between three and seven residues (n = 3, 6 or 7). Structural studies, particularly using NMR spectroscopy have provided an insight into the role and spatial location of residues implicated in receptor binding and biological activity.