Solution conformation of an ET(B) selective agonist, ET-1[Cys(Acm)1,15,Ala3,Leu7,Aib11], in CD3OH/H2O by 1H NMR and molecular modelling.
To 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 alpha-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.
Hewage
C M
CM
Department of Chemistry, University of Edinburgh, UK.
Jiang
L
L
Parkinson
J A
JA
Ramage
R
R
Sadler
I H
IH
D000595:Amino Acid Sequence; D019187:Cadmium Compounds; D019332:Endothelin-1 / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D017433:Protein Structure, Secondary; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists*; D012996:Solutions; D013696:Temperature; D014867:Water
D019187:Cadmium Compounds; D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D012996:Solutions; C112014:endothelin-1, Cys(Acm)(1,15)-Ala(3)-Leu(7)-Aib(11)-; D014867:Water