How do peptides interact with lipid membranes and how does this affect their biological activity?
1. A short review is given of the chemical, physical, and pharmacological development of the idea that target cell lipid membranes may catalyze the interaction between regulatory peptides (or other pharmacologic agents) and their cell surface receptors. 2. The message-address and the membrane compartments concepts explain the observed correlations between the three-dimensional structures of peptides induced by a membrane surface and their preference for a certain receptor subtype. 3. Examples are given for opioid peptides (enkephalin, dynorphin, etc.), tachykinin peptides (substance P, neurokinin A, etc.), and melanocortin peptides (ACTH, alpha-MSH, etc.). 4. Relationships between the conformation of substance P induced by membrane association and that of a non-peptide substance P mimetic are discussed. Possible reasons for the difference between agonistic and antagonistic properties in the peptide field are revealed by this case.
Schwyzer
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R
Swiss Federal Institute of Technology, Bülach.
D000818:Animals; D004347:Drug Interactions; D006801:Humans; D008024:Ligands; D008563:Membrane Lipids / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D018000:Receptors, Peptide / Q000737:chemistry / Q000187:drug effects; D013329:Structure-Activity Relationship
D008024:Ligands; D008563:Membrane Lipids; D010455:Peptides; D018000:Receptors, Peptide