Beta-sheet is the bioactive conformation of the anti-angiogenic anginex peptide
| Autor: | Arjan W. Griffioen, Ruud P.M. Dings, Judy Haseman, Nathan A. Lockwood, Loes I. van Eijk, Monica M. Arroyo, Kevin H. Mayo |
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| Rok vydání: | 2003 |
| Předmět: |
Magnetic Resonance Spectroscopy
Angiogenesis Stereochemistry Beta sheet Peptide Angiogenesis Inhibitors Biochemistry Protein Structure Secondary Molecule Humans Amino Acid Sequence Receptor Molecular Biology Cells Cultured chemistry.chemical_classification Circular Dichroism Anti angiogenic Proteins Cell Biology Endothelial stem cell chemistry Apoptosis Endothelium Vascular Peptides Cell Division Research Article |
| Zdroj: | The Biochemical journal. 373(Pt 1) |
| ISSN: | 0264-6021 |
| Popis: | Anginex is a designed peptide 33mer that functions as a cytokine-like agent to inhibit angiogenesis. Although this short linear peptide has been shown by NMR and CD to form a nascent β-sheet conformation in solution, the actual bioactive structure formed upon binding to its receptor on the surface of endothelial cells could be quite different. By using a series of double-cysteine disulphide-bridged analogues, we provide evidence in the present study that the β-sheet is in fact the bioactive conformation of anginex. CD and NMR spectral analysis of the analogues indicate formation of a β-sheet conformation. Three functional assays, endothelial cell proliferation, apoptosis and in vitro angiogenesis, were performed on all analogues. As long as the placement of disulphide bonds preserved the β-strand alignment, as in the proposed bioactive conformation, bioactivities were preserved. Knowledge of the bioactive conformation of anginex will aid in the design of smaller molecule mimetics of this potent anti-angiogenic peptide. |
| Databáze: | OpenAIRE |
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