Protein Engineering, Vol. 15, No. 3, 161-167,
March 2002
© 2002 Oxford University Press
Design of ETB receptor agonists: NMR spectroscopic and conformational studies of ET7–21[Leu7, Aib11, Cys(Acm)15]
1 Department of Biochemistry, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland, 2 Department of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ 3 Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow G1 1XL, UK
In a previous report we have shown that the endothelin-B receptor-selective linear endothelin peptide, ET-1[Cys (Acm)1,15, Ala3, Leu7, Aib11], folds into an 
-helical conformation in a methanol-d3/water co-solvent [Hewage et al. (1998) FEBS Lett., 425, 234–238]. To study the requirements for the structure–activity relationships, truncated analogues of this peptide were subjected to further studies. Here we report the solution conformation of ET7–21[Leu7, Aib11, Cys(Acm)15], in a methanol-d3/water co-solvent at pH 3.6, by NMR spectroscopic and molecular modelling studies. Further truncation of this short peptide results in it displaying poor agonist activity. The modelled structure shows that the peptide folds into an -helical conformation between residues Lys9–His16, whereas the C-terminus prefers no fixed conformation. This truncated linear endothelin analogue is pivotal for designing endothelin-B receptor agonists.