Effect of permethylation on the haemolytic activity of melittin.

The cytolytic activity of the bee venom toxin, melittin, is abolished on permethylation of the ammonium groups into quaternary trimethylammonium groups. The loss of activity in permethylated melittin may result partly from the absence of the hydrogen bonding potential and partly from steric effects involving the bulky trimethylammonium groups. Displacing the trimethylammonium groups away from the backbone to relieve steric effects (by acylating melittin with glycine or 5-aminopentanoic acid followed by permethylation) restored moderate activity at 5-fold increase in concentration.