DETERMINATION OF THE SECONDARY STRUCTURE OF SELECTED MELITTIN ANALOGSWITH DIFFERENT HEMOLYTIC ACTIVITIES

In earlier studies, we have reported that minor modifications in the a mino acid sequence of melittin result in dramatic changes in its biolo gical activity. In the current study, we have investigated the seconda ry structure of melittin analogues with either increased or decreased haemolytic activity in order to further our understanding of the struc tural features involved in the binding and/or insertion of peptides in to a phospholipid membrane from solution. This was accomplished by ana lysing the c.d. spectra of the analogues in solutions of various ionic strength and, separately, in the presence of micelles. These studies permit the assessment of the effect of small sequence modifications (i .e. single amino acid omission or substitution) on the self-associatio n-induced secondary structure of melittin in aqueous solution, as well as its binding affinity to micelles. It was found that amphipathicity , as well as interchain distances and the orientation of hydrophobic r esidues, were involved in the induction of stabilized structures.