Permeation of model membranes by Peptaibolin mimetics bearing different α,α-dialkylglycines

Abstract

It is reported the membrane permeation studies of a model peptide, Peptaibolin (Ac-Leu-Aib-Leu-Aib-Phol), which is the shortest member of the peptaibols family, and several mimetics incorporating unnatural α,α- dialkylglycines (Deg, Dpg, Ac6c) at the native Aib positions. The model membranes were based on small unilamellar vesicles composed of phosphatidylcholines (egg lecithin, DPPC), phosphatidylglycerols (DPPG, DOPG) and cholesterol, at different compositions and ratios, containing a fluorescent probe encapsulated in their aqueous interior, in order to monitor the permeation process by fluorescence spectroscopy. The obtained results revealed a correlation between the length and bulk of the side chain of the unnatural α,α-dialkylglycines and the ability of the corresponding peptide to permeate the model membranes.