Biochemistry and Biotechnology
Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
The 27-residue polypeptide ω-conotoxin GVIA (ω-CgTx), from the venom of the cone shell Conus geographus, blocks N-type neuronal calcium channels. It contains three disulphide bridges. We reporte here the synthesis and biological characterization of a seires of analogues in which one disulphide has been replaced by substitution of appropriate Cys residues with Ser, viz. [Ser1,16]-ω-CgTx, [Ser8,19]-ω-CgTx, [Ser15,26]-ω-CgTx, [Ser16]-ω-CgTx8-27 and [Ser15]-ω-CgTx1-19. All syntheses were conducted manually using either Boc or Fmoc methodology. Deprotected peptides were oxidized to their bridged forms using either aerial oxidation or aqueous dimethyl sulphoxide. Peptides were purified using RP-HPLC, and their purity and identity were checked by RP-HPLC, capillary electrophoresis and mass spectrometry. Inhibition of neuronal N-type calcium channels was assessed as the inhibition of the twitch responses of rat vas deferens stimualted with single electrical pulses at 20 second intervals. None of these analogues was biologically active, suggesting that the disulphides play an important role in maintaining biological activity.
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