Interaction of adrenocorticotropin-(11-24)-tetradecapeptide with neutral lipid membranes revealed by infrared attenuated total reflection spectroscopy.

Infrared attenuated total reflection spectroscopy (IR-ATR) revealed that the hydrophilic adrenocorticotropin-(11-24)-tetradecapeptide ( ACTH11 -24, net charge 6+) assumed an irregular secondary structure when incorporated into the aqueous layers between equilibrated multibilayers of planar membranes prepared from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine ( POPC ). This structure was characterized by a perpendicular orientation of the peptide bonds on the bilayer surfaces, as observed earlier for the corresponding segment of adrenocorticotropin-(1-24)-tetracosapeptide (ACTH1-24, 6+). Once incorporated, ACTH11 -24 was not removed by washing, in agreement with its strong positive charge. In contrast to ACTH1-24, ACTH11 -24 was not measurably adsorbed to the neutral membranes from 0.1 mM aqueous solutions. The more hydrophobic adrenocorticotropin-(1-10)-decapeptide is also not adsorbed. We therefore concluded that adsorption of ACTH1-24 to neutral membranes was dependent on its amphiphilic primary (amphipathic primary) structure that resulted from the covalent combination of the hydrophobic ACTH1-10 segment with the hydrophilic ACTH11 -24 segment. This conclusion was consistent with the results obtained by vesicle-mediated hydrophobic photolabeling and equilibrium dialysis.