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Volume 270, Number 28, Issue of July 14, pp. 16796-16802, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.

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J. Michael McIntosh , Arik Hasson , Micha E. Spira , William R. Gray , Wenqin Li , Maren Marsh , David R. Hillyard , Baldomero M. Olivera

Conus peptides, including -conotoxins and -conotoxins (targeting calcium channels and nicotinic acetylcholine receptors, respectively) have been useful ligands in neuroscience. In this report, we describe a new family of sodium channel ligands, the µO-conotoxins. The two peptides characterized, µO-conotoxins MrVIA and MrVIB from Conus marmoreus potently block the sodium conductance in Aplysia neurons. This is in marked contrast to standard sodium channel blockers that are relatively ineffective in this system. The sequences of the peptides are as follows.

On-line formulae not verified for accuracy

On-line formulae not verified for accuracy

µO-conotoxin MrVIA was chemically synthesized and proved indistinguishable from the natural product. Surprisingly, the µO-conotoxins show no sequence similarity to the µ-conotoxins. However, ananalysis of cDNA clones encoding the µO-conotoxin MrVIB demonstrated striking sequence similarity to - and -conotoxin precursors. Together, the -, -, and µO-conotoxins define the O-superfamily of Conus peptides. The probable biological role and evolutionary affinities of these peptides are discussed.

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