A New Peptide from the Venom of the Madagascar Cat-Eyed Snake <i>Madagascarophis colubrinus</i> Blocks Nicotinic Acetylcholine Receptor

Abstract

In screening the venoms of various snake species, we found that the venom of the Madagascar cat-eyed snake Madagascarophis colubrinus competes with α-bungarotoxin for binding to the nicotinic acetylcholine receptor from Torpedo californica. Using liquid chromatography, a peptide, called macoluxin and inhibiting the binding of the toxin to the receptor, was isolated from the venom. The amino acid sequence of this 23-amino acid peptide was determined by automatic Edman degradation. Comparison with amino acid sequences of known proteins showed that the macoluxin sequence is homologous to the α-helical region of the sequence of snake venom metalloproteinases. The peptide was synthesized by solid-phase peptide synthesis, and the study of its biological activity showed that it inhibits the binding of α-bungarotoxin to the Torpedo receptor with an IC50 of 47 μM. Macoluxin also reversibly inhibited acetylcholine-induced currents in the muscle-type nicotinic acetylcholine receptor. This is the first data on the presence in the venom of rear fanged snakes of a peptide that can inhibit the nicotinic acetylcholine receptor.