Transfer of peptide hormones from aqueous to membrane phases

Peptide hormones and neurotransmitters are functional amphiphilic substances that deploy their chared and nonpolar substituents as required for traversing aqueous phases en rout to their ultimate transfer into the lipid‐rich environment of their membrane‐embedded receptors. As a means of determining the role(s)that cellular membrane lipids may play in mediating these events, we describe an experimental approach, using high‐resolution 1H‐and 13C‐nmr spectroscopy, for delineation of the structures of complexes between the (neurotransmitter pentapeptide) enkephalins and micellar and vesicular phospholipid particles. Residue‐specific enkephalin interactions with lipid are identified; affinity constants for the hydrophobic component(s) of peptide/lipid association are calculated for enkephalin and several of its analogs; and comparisons with morphine are presented. Finally, based on molecular details obtained from nmr experiments, a model is proposed for the encoutner of a peptide hormone with a phospholipid membrane surface.