The hexacosapeptide melittin I, which is the main toxin of bee venom, has been synthesized by Lübke and Schröder. In addition, the following derivatives have been prepared which are probably also present in bee venom: melittin II (which differs by one serine), and N₁-formylated melittin I and II.

In pharmacological tests, the four synthetic peptides were qualitatively indistinguishable from natural melittin as prepared from bee venom. Theyhemolyzed rabbit erythrocytes with a flat dose-response curve. Melittin I exerted 92% of the activity of the natural substance, the three other peptides 90, 61 and 52% respectively.-Theirsurface activity was between 86 and 96% of that of the natural material.-In contrast to our previous reports, no differences were found in onset, degree and duration of the shortlastinghypotensive action in rabbits.-Toxicity (LD 50, mice) was about 4 mg/kg for natural melittin and for the synthetic melittins I and II. The toxicity of formylated melittins was not very different.-The five compounds caused a slow and prolongedcontraction of the guinea-pig ileum which led to tachyphylaxis.

Peptide mapping confirmed the identity between the main compound of natural melittin and synthetic melittin I. The peptide pattern of synthetic melittin II is different and is further modified by the presence of the N-formyl group.

Our findings leave no doubt as to the identity between the bulk of natural melittin and melittin I. They corroborate the presence in natural melittin of small amounts of N₁-formylated melittin I. The pharmacological similarities to synthetic melittin II and N₁-formylated melittin II (which have not yet been identified in the venom) argue for a broader structural basis of the melittins as a group.