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
-
- Nuclear Magnetic Resonance, Biomolecular
- Animals
- Conotoxins/chemistry*
- Conotoxins/pharmacology
- Embryo, Nonmammalian/metabolism
- Peptides, Cyclic/chemistry*
- Peptides, Cyclic/pharmacology
- Conus Snail/metabolism*
- Models, Molecular
- Oligopeptides/chemistry*
- Oligopeptides/pharmacology
- Amino Acid Sequence
- Molecular Sequence Data
- Zebrafish
- Heart Rate/drug effects
- Protein Conformation
- PubMed
- 20385188 Full text @ Peptides
Citation
Miloslavina, A., Ebert, C., Tietze, D., Ohlenschläger, O., Englert, C., Görlach, M., and Imhof, D. (2010) An unusual peptide from Conus villepinii: synthesis, solutiuon structure, and cardioactivity. Peptides. 31(7):1292-1300.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping