Contryphan-Bt: A pyroglutamic acid containing conopeptide isolated from the venom of Conus betulinus

Abstract

A new member of the contryphans family was isolated from the venom of Conus betilinus, a vermivorous species distributed in the South China Sea. Its sequence, ZSGCO(D-W)KPWC-NH₂ (Z, pyroglutamic acid), was established by a combination of de novo MS/MS sequencing and venom-duct transcriptome sequencing. The occurrence of D-Trp⁶ was confirmed by chemical synthesis and HPLC behavior comparison. Like known contryphans, contryphan-Bt produces the "stiff-tail" syndrome in mice and contains one disulfide bond, a hydroxyproline, a D-tryptophan, and an amidated C-terminus. However, contryphan-Bt differs from previously identified contryphans by a pyroglutamic acid at the N terminus. CD spectrum reveals that contryphan-Bt possess β-turn in solution.

Keywords: Conopeptide; Contryphan; Contryphan-Bt; Conus betulinus; Pyroglutamic acid.