Solving the [alpha]-conotoxin folding problem: efficient selenium-directed on-resin generation of more potent and stable nicotinic acetylcholine receptor antagonists

The application of selenocysteine in a supported phase method to direct native folding and produce [alpha]-conotoxins efficiently with improved biophysical properties is reported. The results obtained provide insight into the development of more stable and potent nicotinic antagonists suitable for new drug therapies, and highlight the application of selenocysteine technology more broadly to disulfide-bonded peptides and proteins.