Aromatic substitutions in alpha-conotoxin ImI. Synthesis of iodinated photoactivatable derivative

Conotoxin ImI is a specific marker of alpha 7 nicotinic acetylcholine recep tors. To study the role of aromatic indole group of tryptophan 10 in biolog ical activity of ImI, the analogue containing tyrosine at this position was synthesized by solid-phase peptide synthesis. The analogue obtained, as we ll as its iodinated derivatives, were shown to be active against rat brain alpha 7 acetylcholine receptor expressed in Xenopus oocytes. Attachment of bulky aromatic p-benzoylbenzoyl group to N-terminal alpha-amino group of io dinated [Tyr(10)]ImI only slightly affected the biological activity of the analogue. The data obtained suggest that indole ring of tryptophan 10 is no t absolutely necessary for biological activity of conotoxin ImI, and that t he N-terminus can accommodate a large aromatic group without loss of biolog ical activity. (C) 1999 Elsevier Science Ltd. All rights reserved.