SPIN-LABEL AND H-2-NMR STUDIES ON THE INTERACTION OF MELANOTROPIC PEPTIDES WITH LIPID BILAYERS

The interaction of the cationic tridecapeptide alpha-melanocyte stimul ating hormone (alpha-MSH) and the biologically more active analog [Nle (4), DPhe(7)]-alpha-MSH with lipid membranes was investigated by means of ESR of spin probes incorporated in the bilayer, and NMR of deutera ted lipids. All spin labels used here, stearic acid and phospholipid d erivatives labeled at the 5(th) and 12(th) position of the hydrocarbon chain, and the cholestane label, incorporated into anionic vesicles o f DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) in the liquid-cr ystalline phase, indicated that both peptides decrease the motional fr eedom of the acyl chains. No peptide effect was detected with neutral lipid bilayers. Changes in the alpha-deuteron quadrupolar splittings a nd spin lattice relaxation time of DMPG deuterated at the glycerol hea dgroup paralleled the results obtained with ESR, showing that the pept ides cause a better packing both at the headgroup and at the acyl chai n bilayer regions. The stronger effect caused by the more potent analo g in the membrane structure, when compared to the native hormone, is d iscussed in terms of its larger lipid association constant and/or its deeper penetration into the bilayer.