Membrane Permeability of Hydrocarbon-Cross-Linked Peptides

摘要: Schafmeister, Po, and Verdine (another study) introduced a method using hydrocarbon linker (staple) to stabilize peptide in helical configuration. One intended goal of this scheme is facilitate the delivery drugs into target cells. Here, we investigate whether stapled peptides are intrinsically membrane permeable, by performing case study on 12-mer named NYAD-1. We found that native CAI (an HIV-1 inhibitor) does not bind lipid bilayers, however NYAD-1 indeed permeates through bilayers even at low solution concentrations. To understand reason for permeability, investigated physical properties as function bound peptide/lipid molar ratio P/L. spontaneously binds bilayer. At P/L, primarily polar-apolar interface with its axis parallel bilayer, which has effect stretching area thinning membrane. The reaches maximum P/L ∼1/15–1/12 DOPC bilayers. Additional have little their axes normal plane Thus, interaction behavior similar antimicrobial peptides, such magainin melittin. emphasize all α-helical form behave way.