1H nuclear magnetic resonance studies of the conformations of adrenocorticotropic hormone ACTH(1–10) and related peptides in aqueous and trifluoroethanol solutions

Abstract

We have measured the 270 M Hz ¹H n.m.r. spectra of adrenocorticotropic hormone ACTH (1–10) and related peptides in aqueous and trifluoroethanol solution at a series of temperatures. In aqueous solution the J_NC coupling constants (between α-CH and NH protons) and the temperature dependence of the peptide NH proton chemical shifts indicate that there is a random coil mixture of conformations. Shielding interactions between the side-chains of the aromatic residues L-Phe-7 and L-Trp-9 are observed and shown to be expected from a random coil mixture of conformations where the side-chains of alternate residues are close together in some conformations. In trifluoroethanol solutions, the data indicate that the overall conformation of ACTH (1–10) is displaced somewhat from the random coil mixture: while the J_NC coupling constants indicate that there is not a dominant contribution from helical conformations, some contribution from these forms is suggested by the presence of some intramolecular hydrogen bonding involving peptide NH protons.