| Abstract: | Fluorescence spectroscopy results show that the α-melanocyte-stimulating hormone peptide (α-MSH) interacts with acidic lipid vesicles. Detectable structural changes are concomitant with the passage of a tryptophan residue from aqueous to lipidic media. The observed multiexponential decay of fluorescence, rationalized as originating from three rotameric populations of the tryptophan residue, has been used together with a matrix algorithm to find the most probable conformational families of α-MSH in water and lipid environments. A model is discussed in which the same conformational families occur in various phases, although with different probabilities. A conformational family in which χ1 of the Trp9 side chain is in the trans-rotameric conformation is shown to have structural features highly appropriate to interact with negatively charged biological membranes, which are also in accordance with previous molecular dynamics simulations and with structures engineered in α-MSH analogs that show an increased potency in biological essays. The gauche minus and gauche plus side-chain conformations of Trp9, on the other hand, yield conformations more likely to predominate in aqueous solution. NMR spectroscopy measurements of α-MSH analogs indicate the existence in aqueous solution of a β strand in the vicinity of Trp9. A similar structural feature was found in the present conformational analysis for the gauche minus and gauche plus side-chain rotamers of Trp9. © 1995 John Wiley & Sons, Inc. |
