CHARACTERIZATION OF STRUCTURAL TRANSITIONS FROM AQUEOUS-SOLUTION TO ALIPID PHASE FOR ALPHA-MSH

Fluorescence spectroscopy results show that the alpha-melanocyte-stimu lating hormone peptide (alpha-MSH) interacts with acidic lipid vesicle s. Detectable structural changes are concomitant with the passage of a tryptophan residue from aqueous to lipidic media. The observed multie xponential decay of fluorescence, rationalized as originating from thr ee rotameric populations of the tryptophan residue, has been used toge ther with a matrix algorithm to find the most probable conformational families of alpha-MSH in water and lipid environments. A model is disc ussed in which the same conformational families occur in various phase s, although with different probabilities. A conformational family in w hich chi(1) of the Trp9 side chain is in the trans-rotameric conformat ion is shown to have structural features highly appropriate to interac t with negatively charged biological membranes, which are also in acco rdance with previous molecular dynamics simulations and with structure s engineered in alpha-MSH analogs that show an increased potency in bi ological essays. The gauche minus and gauche plus side-chain conformat ions of Trp9, on the other hand, yield conformations more likely to pr edominate in aqueous solution. NMR spectroscopy measurements of alpha- MSH analogs indicate the existence in aqueous solution of a beta stran d in the vicinity of Trp9. A similar structural feature was found in t he present conformational analysis for the gauche minus and gauche plu s side-chain rotamers of Trp9. (C) 1995 John Wiley & Sons, Inc.