PRIMARY STRUCTURAL MOTIFS OFConus PEPTIDES

Abstract

The venoms of predatory marine snails of the family Conidae are complex mixtures of proteins, peptides and smaller molecules; most biological activities are associated with peptides ranging in size from ~13 to 30 amino acid residues. Since the isolation of the first a-conotoxin from Conus geographus (Cruz et al., 1976), the structures and mode of action of many peptides from Conus venom have been elucidated (Myers et al., 1993). Among these are the μ- and δ-conotoxins that act on voltage-sensitive sodium channels (Cruz et al., 1985; Hillyard et al., 1989; Sato et al., 1983; Shon et al, 1994), the co-conotoxins which inhibit voltage-sensitive calcium channels (Hillyard et al., 1992; Olivera et al., 1987; Olivera et al., 1985; Olivera et al., 1984; Ramilo et al., 1992), the a- and aA-conotoxins which inhibit nicotinic acetylcholine receptors (Gray et al., 1981; Hopkins et al., 1995; Macintosh et al., 1982; Myers, 1989; Ramilo et al., 1992; Zafaralla et al., 1988) and the conantokins that inhibit glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype (Haack et al., 1990; Mcintosh et al., 1984; Mena et al., 1990). It is now estimated that each Conus venom may contain 50 to 200 peptides. Since there are ∼500 species, even a conservative projection of the total number of biologically-active peptides in the venom of this genus is a staggering 25,000. Indeed, the Conus system has continued to provide new peptide ligands with novel structures and pharmacological action.