Benzophenone-Type Photoactivatable Derivatives of α-Neurotoxins and α-Conotoxins in Studies on Torpedo Nicotinic Acetylcholine Receptor

Abstract

By chemical modification of different lysine residues, benzoylbenzoyl (BzBz) groups were introduced into neurotoxin II Naja naja oxiana (NT-II), a short-chain snake venom α-neurotoxin, while p-benzoylphenylalanyl (Bpa) residue was incorporated in the course of peptide synthesis at position 11 of α-conotoxin G1, a neurotoxic peptide from marine snails. Although the crosslinking yields for iodinated BzBz derivatives of NT-II and for Bpa analogue of G1 to the membrane-bound Torpedo californica nicotinic acetylcholine receptor (AChR) are relatively low, the subunit labeling patterns confirm the earlier conclusions, derived from arylazide or diazirine photolabels, that α-neurotoxins and α-conotoxins bind at the subunit interfaces. Detecting the labeled α-subunit with iodinated Bpa analogue of G1 provided a direct proof for the contact between this subunit and α-conotoxin molecule.