A NEW CONUS PEPTIDE LIGAND FOR CA CHANNEL SUBTYPES

A cDNA clone encoding a new omega-conotoxin was identified from Conus magus. The predicted peptide was chemically synthesized using a novel strategy that efficiently yielded the biologically active disulfide-bo nded isomer. This peptide, omega-conotoxin MVIID, targets other voltag e-gated calcium channels besides the N-subtype and exhibits greater di scrimination against the N-channel subtype than any other omega-conoto xin variant to date. Consequently, omega-conotoxin MVIID may be a part icularly useful ligand for calcium channel subtypes that are not of th e L- or N-subclasses. Of the eight major sequence variants of omega-co notoxins that have been elucidated, four come from Conus magus venom. We suggest that sequence variants from the same venom may be designed to optimally interact with different molecular variants of calcium cha nnels; such omega-conotoxin sets from a single venom may therefore be useful for helping to identify novel calcium channel subtypes.