Solution conformation of an ETB selective agonist, ET-1[Cys(Acm)1,15,Ala3,Leu7,Aib11], in CD3OH/H2O by 1H NMR and molecular modelling

AbstractTo understand the basic structural requirements for the biological activity of endothelin peptides, the solution structure of an ETB selective agonist, ET-1[Cys(Acm)1,15,Ala3,Leu7,Aib11], was investigated by 1H NMR spectroscopy and molecular modelling. The structure is characterised by an α-helical conformation between residues Ser5-His16 but is undefined at both the N and C termini. To date, neither the solution structures of linear modified peptides nor the effects of a methanol/water solvent system have been examined for endothelin or endothelin-like peptides. This structure plays an important role towards the design of endothelin receptor selective agonists and antagonists