Influence of tryptophan residues on melittin's hemolytic activity.
Earlier studies of melittin have shown that the Trp residue at position 19 is significantly involved in its hemolytic activity. Tryptophan residues 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 would have on melittin's hemolytic activity. This was accomplished through 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 extreme of melittin's two alpha-helices, or in its 'hinge' region. Decreases in activity were found upon replacing any of melittin's Leu residues 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 liposomes.
Torrey Pines Institute for Molecular Studies, San Diego, CA 92121.
S E
SE
Blondelle
L R
LR
Simpkins
E
E
Pérez-Payá
R A
RA
Houghten
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D008555:Melitten / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000096:biosynthesis / Q000737:chemistry; D012984:Software; D014364:Tryptophan / Q000737:chemistry*
D009842:Oligopeptides; D008555:Melitten; D014364:Tryptophan