Membrane structure and biologic activity of adrenocorticotropin (ACTH) and melanotropin (MSH) peptides. Estimation of structural parameters including the influence of the helix dipole moment

Estimation of preferred conformation, orientation, and accumulation of adrenocorticotropin (1–24)‐peptide at an aqueous‐hydrophobic interface produced a model that agreed with that developed from experimental observations with lipid membranes. Thus, the N‐terminal message segment (residues 1–11) was incorporated into the hydrophobic phase as an α‐helical, perpendicularly oriented domain with an apparent dissociation constant of ca. 5 · 10−5 M. The C‐terminal address segment (residues 12‐24) remained in the aqueous phase as a random‐coil domain. Three parameters proved sufficient to define the model: the Gibbs free energy of hydrophobic association, the molecular amphiphilic moment, and the molecular electric dipole moment. For estimating interactions with biologic membranes (that carry a net negative charge), the Boltzmann distribution of charged peptides was also considered. The estimations were extended to adrenocorticotropin (1‐10)‐peptide and α‐melanotropin. In the first case, the prediction agreed with the earlier observations, in the second, it awaits its experimental proof. The estimated membrane structures were compared with available biologic data. As for opioid peptides, it appears that the amphiphilic moment is an important new parameter for determining quantitative structure‐activity relationships (QSAR) in receptor selection and biologic potency.