Hydrophobic and electrostatic interactions between adrenocorticotropin-(1-24) -tetracosapeptide and lipid vesicles. Amphiphilic primary structures.

Abstract

Hydrophobic photolabeling with 3-(trifluoromethyl) -3-(m-[125I]iodophenyl) diazirine ( [125I]TID [Brunner, J., & Semenza , G. (1981) Biochemistry 20, 7174-7182] ) and equilibrium dialysis were used to study hydrophobic and electrostatic interactions between three adrenocorticotropin fragments and liposomes prepared from mixtures of phosphatidylcholine with phosphatidic acid or phosphatidylserine. Corticotropin-(1-10)-decapeptide (ACTH1-10, net charge 0) formed hydrophobic clusters with [125I]TID in aqueous solutions at peptide concentrations above 1 microM but did not interact appreciably with neutral or anionic liposomes. Corticotropin -(11-24)-tetradecapeptide ( ACTH11 -24, net charge 6+) reacted electrostatically with anionic liposomes but showed no hydrophobic interactions. Corticotropin-(1-24)-tetracosapeptide (ACTH1-24, net charge 6+), a covalent combination of the two fragments, exhibited both hydrophobic and electrostatic interactions with lipid vesicles. Edman degradation and chymotryptic hydrolysis of labeled ACTH1-24 revealed that the hydrophobic interaction involved the N-terminal decapeptide "message" segment (corresponding to ACTH1-10) which entered the membrane and that the electrostatic interaction was caused by the C-terminal tetradecapeptide "address" segment (corresponding to ACTH11 -24) which remained on the aqueous membrane surface. This surface is in complete analogy to that reported for dynorphin- (1-13)-tridecapeptide by Gysin and Schwyzer [ Gysin , B., & Schwyer , R. (1983) FEBS Lett. 158, 12-16; Gysin , B., & Schwyzer , R. (1983) Arch. Biochem. Biophys. 225, 467-474]: in both cases, the specific, hydrophobic membrane interaction of the "message" critically depended on the presence of the hydrophilic "address". The results reported here were consistent with those obtained by infrared attenuated total reflection spectroscopy [ Gremlich , H.-U., Fringeli , U.-P., & Schwyzer , R. (1983) Biochemistry 22, 4257-4263] and were crucial for their interpretation.(ABSTRACT TRUNCATED AT 250 WORDS)