Synthesis and biological characterisation of a series of iberiotoxin analogues
| Autor: | R. B. Johns, Roger Murphy, Wolfgang Kunze, James A. Angus, James P. Flinn |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Protein Folding
Stereochemistry Guinea Pigs Molecular Sequence Data Myenteric Plexus Scorpion Venoms Peptide Biochemistry Mass Spectrometry Membrane Potentials Structure-Activity Relationship Protein structure Animals Structure–activity relationship Dimethyl Sulfoxide Amino Acid Sequence Disulfides Peptide sequence Chromatography High Pressure Liquid Toxins Biological Alanine chemistry.chemical_classification Biological activity Iberiotoxin Electric Stimulation Protein Structure Tertiary chemistry Protein folding Peptides Oxidation-Reduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0367-8377 |
| DOI: | 10.1111/j.1399-3011.1995.tb01044.x |
| Popis: | We report here the synthesis of iberiotoxin (IbTX), a 37-amino acid peptide containing three disulfide bridges, and a series of mono-looped analogues. All syntheses were conducted using Fmoc chemistry. Synthesis of IbTX gave a product which was indistinguishable from a reference sample in both its physico-chemical properties and its biological activity. A series of three mono-looped analogues, in which four of the six cysteines were replaced by alanine, were synthesised to give [Ala7,13,28,33]-IbTX, [Ala13,17,33,35]-IbTX and [Ala7,17,28,35]-IbTX. Oxidation of the linear form of [Ala7,17,28,35]-IbTX to form the Cys13 to Cys33 disulfide bridge proceeded more slowly than that of the other two analogues. None of these analogues was biologically active, indicating that no single loop is the mediator of channel blocking activity. |
| Databáze: | OpenAIRE |
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