CA2-INDUCED AND AL3+-INDUCED CONFORMATIONAL TRANSITIONS OF AMYLOID FRAGMENT H-ILE-ILE-GLY-LEU-MET-NH2()

The effect of Ca2+ and Al3+ binding on the conformation of the neuroto xic amyloid fragment H-Ile-Ile-Gly-Leu-Met-NH2 [beta A(31-35)NH2] was studied in trifluoroethanol solutions and in the presence of liposomes . Comparative circular dichroism and Fourier-transform infrared spectr oscopic studies revealed that the peptide forms a specific 1:1 complex with Ca2+ which coordinates the polar amide carbonyl groups of the pe ptide backbone. The results suggest the importance of a folded structu re in the complexation of Ca2+. On the contrary, the increasing Al3+ c oncentration causes a gradual shift of the conformational equilibrium toward beta-sheet structure reflecting no specific binding site for Al 3+. In the presence of liposomes the peptide adopts a conformation sim ilar to that of the Ca2+-peptide complex. The relevance of the stabili zation of peptide conformation by Ca2+ and liposome binding to the bio active conformation of beta A(31-35)NH2 is also discussed. (C) 1996 Ac ademic Press, Inc.