INFLUENCE OF TRYPTOPHAN RESIDUES ON MELITTINS HEMOLYTIC-ACTIVITY

Earlier studies of melittin have shown that the Trp residue at positio n 19 is significantly involved in its hemolytic activity. TrYPtophan r esidues have also been reported to play a specific and important role in a number of other biological interactions. In the present study, we investigated what effect the introduction of a second Trp residue wou ld have on melittin s hemolytic activity. This was accomplished throug h the synthesis and analysis of a complete set of 25 single-position, synthetic Trp substitution analogs. Significant increases in activity were observed upon substituting Trp at a single residue at either extr eme of melittin's two alpha-helices, or in its 'hinge' region. Decreas es in activity were found upon replacing any of melittin's Leu residue s with Trp. The changes in activity of all of the analogs relative to melittin were found to be correlated to their behavior during RP-HPLC, as was their variation in percent helicity in the presence of liposom es.