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Updated: May 2, 2026

Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
Published on: October 2, 2018
Conformational analysis of a 20-membered cyclic peptide disulfide from Conus virgo with a WPW segment: evidence for
Rajesh Sonti1, K N Shashanka Rao, Sudarshan Chidanand
1Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012 (India), Fax: (+91) 80-3600683; NMR Research Centre, Indian Institute of Science, Bangalore 560012 (India).
Abstract:
A novel peptide containing a single disulfide bond, CIWPWC (Vi804), has been isolated and characterised from the venom of the marine cone snail, Conus virgo. A precursor polypeptide sequence derived from complementary DNA, corresponding to the M-superfamily conotoxins, has been identified. The identity of the synthetic and natural peptide sequence has been established. A detailed analysis of the conformation in solution is reported for Vi804 and a synthetic analogue, CI(D) WPWC ((D) W3-Vi804), in order to establish the structure of the novel WPW motif, which occurs in the context of a 20-membered macrocyclic disulfide. Vi804 exists exclusively in the cis W3P4 conformer in water and methanol, whereas (D) W3-Vi804 occurs exclusively as the trans conformer. NMR spectra revealed a W3P4 type VI β turn in Vi804 and a type II' β turn in the analogue peptide, (D) W3-Vi804. The extremely high-field chemical shifts of the proline ring protons, together with specific nuclear Overhauser effects, are used to establish a conformation in which the proline ring is sandwiched between the flanking Trp residues, which emphasises a stabilising role for the aromatic-proline interactions, mediated predominantly by dispersion forces.
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