Conformations of cyclic pentapeptide endothelin receptor antagonists.
The solution conformations in methanol and chloroform of the endothelin A receptor antagonists cyclo(dV-L-dW-dD-P), 1, and cyclo(dV-N alpha-MeL-dW-dD-P), 2, have been studied by NMR spectroscopy at room temperature and below. In these solvents, both peptides were found to have a well defined peptide backbone conformation composed of a type II beta turn at the Leu-D-Trp and a gamma' turn at Pro. This conformation is in agreement with results reported for 1 in other solvents and consistent with the expected location of the N-methyl substituent in that backbone. In methanol, both peptides show NOE and chemical shift evidence of close contact between the Leu and D-Trp side chains. This interaction is greatly reduced or absent in chloroform, and is stronger in methanol at 203 K than at 298 K.
Bean
J W
JW
Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
Peishoff
C E
CE
Kopple
K D
KD
D000595:Amino Acid Sequence; D065128:Endothelin Receptor Antagonists; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions; D012997:Solvents
D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D012996:Solutions; D012997:Solvents