Influence of spontaneous curvature of membrane-active drugson their insertion into lipid bilayers
The insertion into lipid bilayers plays an important role for many drugs. The spontaneous curvature of lipids has been discussed as having a pronounced influence on how far such guest molecules penetrate into a lipid bilayer. Vice versa, also the spontaneous curvature of amphiphilic guest molecules themselves is expected to direct guest molecules either towards the interior of the membrane or the water/bilayer interface. In this proposal we plan to use a series of amphipathic alpha-helical peptides with different spontaneous curvatures to evaluate the role of this parameter on the depth of insertion into a lipid bilayer. The set of peptides is designed to possess different cross section shapes leading to different spontaneous curvatures. We envisage to compare the insertion depth in bilayers with different lateral pressure profiles, to monitor the interplay of peptide and membrane spontaneous curvature. Following a previous study at ILL (proposal 8-02-827, see corresponding experimental report), we propose to use neutron small angle diffraction on oriented bilayer samples to determine the scattering length density profile across the lipid bilayer.
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GRAGE Stephan and DEME Bruno. (2020). Influence of spontaneous curvature of membrane-active drugson their insertion into lipid bilayers. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.8-02-871
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