Conformation and interactions of bioactive peptides from insect venoms: the bombolitins.

Bombolitins are five structurally related heptadecapeptides originally isolated from the venom of a bumblebee, acting at membrane level and able to enhance the activity of Phospholipase A2. The biological activity of this class of natural peptides seems to be related to the their ability to form amphiphilic helical structures in the presence of phospholipid aggregates or related membrane model systems. We have carried out systematic investigations on a series of bombolitins and their synthetic analogs in order to establish the conditions in which amphipathic helices are formed and to elucidate the details of the interaction with phospholipids and related model systems. We have shown that bombolitins and their analogs interact with phospholipid aggregates and detergent micelles forming amphiphilic helices. By means of the Langmuir film balance technique, coupled with fluorescence microscopy, we have Shown that bombolitins perturbe the structure of phospholipid monolayers, forming phase separated peptide domains. In aqueous solution, in the absence of detergent or phospholipids, bombolitins form oligomeric aggregates with consequent conformational transition from a random coil to an alpha-helical structure. In the aggregate structure, evidence was obtained that helices are oriented in an antiparallel fashion. In this article we summarize the most recent results of conformational studies by CD, NMR and computer simulations on a series of bombolitins and retro-, all-D- and all-D-retro-analogs.