Peptaibolin analogues by incorporation of α,α-dialkylglycines: synthesis and study of their membrane permeating ability

Analogues of Peptaibolin, a peptaibol with antibiotic activity, incorporating α,α-dialkylglycines (Deg, Dpg, and Ac6c) at selected positions were synthesised by MW-SPPS and fully characterized. A control analogue incorporating L-alanine was also prepared. The native peptide and the analogues were studied by fluorescence spectroscopy for their membrane permeating activity. Small unilamellar vesicles (SUVs) of egg phosphatidylcholine/ cholesterol (70:30) containing an encapsulated fluorescence probe (6-carboxyfluorescein) were used as membrane models. The assays of carboxyfluorescein release from SUVs upon peptide addition showed that Peptaibolin-Dpg and Peptaibolin-Ac6c are the most active peptides. These results indicate that the structure of the α,α-dialkylglycines is crucial for the membrane permeating ability of these Peptaibolin analogues.

Fundação para a Ciência e Tecnologia (Portugal)

The authors acknowledge Fundação para a Ciência e a Tecnologia (Portugal) and FEDERCOMPETE-QREN-EU for financial support through projects PTDC/QUI-BIQ/118389/2010 (FCOMP-01-0124-FEDER-020906), PEst-C/QUI/UI0686/2013 (F-COMP-01-0124-FEDER- 037302), PEst-C/FIS/UI0607/2013 (F-COMP-01-0124-FEDER-022711) and the portuguese NMR network (PTNMR, Bruker Avance III 400-Univ. Minho).