PUBLICATION

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

Authors
Miloslavina, A., Ebert, C., Tietze, D., Ohlenschläger, O., Englert, C., Görlach, M., and Imhof, D.
ID
ZDB-PUB-100420-21
Date
2010
Source
Peptides   31(7): 1292-1300 (Journal)
Registered Authors
Englert, Christoph
Keywords
Conopeptide, Oxidation, Ionic liquids, NMR solution structure, Cardioactivity, Zebrafish embryos
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Conotoxins/chemistry*
  • Conotoxins/pharmacology
  • Conus Snail/metabolism*
  • Embryo, Nonmammalian/metabolism
  • Heart Rate/drug effects
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Oligopeptides/chemistry*
  • Oligopeptides/pharmacology
  • Peptides, Cyclic/chemistry*
  • Peptides, Cyclic/pharmacology
  • Protein Conformation
  • Zebrafish
PubMed
20385188 Full text @ Peptides
Abstract
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. The linear precursor peptide was generated by standard solid phase synthesis. Oxidation of the cysteine residues to yield the disulfide-bridged peptide was investigated under different conditions, including several ionic liquids (ILs) as new biocompatible reaction media. Among the examined ILs, 1-ethyl-3-methylimidazolium tosylate ([C(2)mim][OTs]) was most efficient for CCAP-vil oxidative folding, since oxidation occurred without any byproduct formation. The structure of CCAP-vil was determined by NMR methods in aqueous solution and revealed a loop structure adopting a type(I) square-turn between residues 4-7 imposed by the flanking disulfide bridge. The amino acid side chains of Pro(1), Phe(2), Phe(6) and Tyr(9) point in three directions away from the cyclic core into the solvent creating a rather hydrophobic surface of the molecule. Based on sequence homology to cardioactive peptides (CAPs) from gastropods and arthropods, such as PFc[CNAFTGC]-NH(2) (CCAP), the influence of CCAP-vil on heart rate using zebrafish embryos was investigated. CCAP-vil reduced the heart rate immediately upon injection into the heart as well as upon indirect application indicating an opposite effect to the cardioaccelerating CCAP.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping