Reference : Insight into the cellular uptake mechanism of a secondary amphipathic cell penetrating p...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/63111
Insight into the cellular uptake mechanism of a secondary amphipathic cell penetrating peptide for siRNA delivery.
English
Konate, K. [> > > >]
Crombez, L. [> > > >]
Deshayes, S. [> > > >]
Decaffmeyer, M. [> > > >]
Thomas, Annick [Université de Liège - ULg > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie moléc. et numér. >]
Brasseur, Robert mailto [Université de Liège - ULg > > Gembloux Agro-Bio Tech >]
Aldrian, G. [> > > >]
Heitz, F. [> > > >]
Divita, G. [> > > >]
2010
Biochemistry
American Chemical Society
Yes (verified by ORBi)
0006-2960
1520-4995
Washington
DC
[en] Delivery of siRNA remains a major limitation to their clinical application and several technologies have been proposed to improve their cellular uptake. We recently described a peptide-based nanoparticle system for efficient delivery of siRNA into primary cell lines: CADY. CADY is a secondary amphipathic peptide that forms stable complexes with siRNA and improves their cellular uptake independently of the endosomal pathway. In the present work, we have combined molecular modelling, spectroscopy and membrane interaction approaches, in order to gain further insight into CADY/siRNA particle mechanism of interaction with biological membrane. We demonstrate that CADY forms stable complexes with siRNA and binds phospholipids tightly, mainly through electrostatic interactions. Binding to siRNA or phospholipids triggers a conformational transition of CADY from an unfolded state to an -helical structure, thereby stabilizing CADY/siRNA complexes and improving their interactions with cell membranes. Therefore, we propose that CADY cellular membrane interaction is driven by its structural polymorphism which enables stabilization of both electrostatic and hydrophobic contacts with surface membrane proteoglycan and phospholipids.
http://hdl.handle.net/2268/63111
10.1021/bi901791x

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