Two new 4-Cys conotoxins (framework 14) of the vermivorous snail Conus austini from the Gulf of Mexico with activity in the central nervous system of mice

As part of continuing studies of the venom components present in Conus austini (syn.: Conus cancellatus), a vermivorous cone snail collected in the western Gulf of Mexico, Mexico, two major peptides, as14a and asl4b, were purified and characterized. Their amino acid sequences were determined by automatic Edman sequencing after reduction and alkylation. Their molecular masses, established by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, confirmed the chemical analyses and indicated that as14a and as14b have free C-termini. Each peptide contains 4-Cys residues arranged in a pattern (C-C-C-C, framework 14). The primary structure of asl4a is GGVGRCIYNCMNSGGGLNFIQCKTMCY (experimental monoisotopic mass 2883.92 Da; calculated monoisotopic mass 2884.20 Da), whereas that of asl4b is RWDVDQCIYYCLNGVVGYSYTECQTMCT (experimental monoisotopic mass 3308.63 Da; calculated monoisotopic mass 3308.34 Da). Both purified peptides elicited scratching and grooming activity in mice, and asl4b also caused body and rear limb extension and tail curling immediately upon injection. The high sequence similarity of peptide asl4a with peptide vil14a from the vermivorous C. villepinii suggests that the former might block K+ channels. (c) 2007 Elsevier Inc. All rights reserved.