CONFORMATIONS OF CYCLIC PENTAPEPTIDE ENDOTHELIN RECEPTOR ANTAGONISTS

The solution conformations in methanol and chloroform of the endotheli n 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 tempera ture 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 i n agreement with results reported for 1 in other solvents and consiste nt with the expected location of the N-methyl substituent in that back bone. In methanol, both peptides show NOE and chemical shift evidence of close contact between the Leu and D-Trp side chains. This interacti on is greatly reduced or absent in chloroform, and is stronger in meth anol at 203 K than at 298 K. (C) Munksgaard 1994.