beta-Sheet is the bioactive conformation of the anti-angiogenic anginex peptide

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.