STRUCTURE AND ACTIVITY STUDIES OF PARDAXIN AND ANALOGS USING MODEL MEMBRANES OF PHOSPHATIDYLCHOLINE

Thirteen synthetic pardaxin analogues were assayed for their ability to interact with model membranes of phosphatidylcholine. The results suggested the following: An amphipathic alpha-helix from isoleucine-14 to leucine-26 is responsible for most of the membrane perturbing properties of pardaxin. A hydrophobic N-terminal region enhances the activity of the isoleucine-14 to leucine-26 alpha-helix by binding the pardaxin molecule to the lipid bilayer. A bend centered around 12Ser-13Pro appears to create overall amphipathicity for the two different helical regions of pardaxin, but this contributes only slightly to potency. The C-terminal amino acids are unimportant for membrane perturbing activity and may be present only to enhance transportation in an aqueous environment prior to membrane binding in the native system.