Conformational Analysis of a 20‐Membered Cyclic Peptide Disulfide from Conus virgo with a WPW Segment: Evidence for an Aromatic–Proline Sandwich |
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| Authors: | Rajesh Sonti K. N. Shashanka Rao Sudarshan Chidanand Dr. Konkallu Hanumae Gowd Dr. Srinivasarao Raghothama Prof. Padmanabhan Balaram |
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| Affiliation: | 1. Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012 (India), Fax: (+91)?80‐3600683;2. NMR Research Centre, Indian Institute of Science, Bangalore 560012 (India);3. UG Centre, Indian Institute of Science, Bangalore 560012 (India) |
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| 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, CIDWPWC (DW3‐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 W3?P4 conformer in water and methanol, whereas DW3‐Vi804 occurs exclusively as the trans conformer. NMR spectra revealed a W3?P4 type VI β turn in Vi804 and a type II′ β turn in the analogue peptide, DW3‐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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| Keywords: | amino acids aromatic– proline interactions beta turns disulfides peptides |
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