Molecular determinants for the subtype specificity of μ-conotoxin SIIIA targeting neuronal voltage-gated sodium channels.

Voltage-gated sodium channels (Na(V) channels) play a pivotal role in neuronal excitability; they are specifically targeted by μ-conotoxins from the venom of marine cone snails. These peptide toxins bind to the outer vestibule of the channel pore thereby blocking ion conduction through Na(V) channels. μ-Conotoxin SIIIA from Conus striatus was shown to be a potent inhibitor of neuronal sodium channels and to display analgesic effects in mice, albeit the molecular targets are not unambiguously known.

An unusual peptide from Conus villepinii: synthesis, solution structure, and cardioactivity.

The venom of marine cone snails contains a variety of conformationally constrained peptides utilized by the animal to capture prey. Besides numerous conotoxins, which are characterized by complex disulfide patterns, other peptides with only a single disulfide bridge were isolated from different conus species. Here, we report the synthesis, structure elucidation and biological evaluation of the novel C-terminally amidated decapeptide CCAP-vil, PFc[CNSFGC]YN-NH(2), from Conus villepinii.

A room temperature ionic liquid as convenient solvent for the oxidative folding of conopeptides.

We report the first example of conopeptide oxidation performed in a biocompatible ionic liquid, 1-ethyl-3-methylimidazolium acetate ([C(2)mim][OAc]), which enables the efficient formation of both hydrophilic and poorly water-soluble conotoxins compared with conventional methods. Moreover, the method features a high-concentration approach ultimately leading to higher yields at reduced separation effort.