Reference : Modeling of non-covalent complexes of the cell-penetrating peptide CADY and its siRNA ca...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/134944
Modeling of non-covalent complexes of the cell-penetrating peptide CADY and its siRNA cargo.
English
Crowet, Jean-Marc mailto [Université de Liège - ULg > Chimie et bio-industries > Biophysique moléc. numér. >]
Lins, Laurence mailto [Université de Liège - ULg > Chimie et bio-industries > Biophysique moléc. numér. >]
Deshayes, Sebastien [> >]
Divita, Gilles [> >]
Morris, May [> >]
Brasseur, Robert mailto [Université de Liège - ULg > Chimie et bio-industries > Biophysique moléc. numér. >]
Thomas, Annick [Université de Liège - ULg > Chimie et bio-industries > Biophysique moléc. numér. >]
2012
Biochimica et Biophysica Acta
Yes (verified by ORBi)
International
0006-3002
[en] CADY is a cell-penetrating peptide spontaneously making non-covalent complexes with siRNAs in water. Neither the structure of CADY nor that of the complexes is resolved. We have calculated and analyzed 3D models of CADY and of the non-covalent CADY-siRNA complexes in order to understand their formation and stabilization. Data from the ab initio calculations and molecular dynamics support that, in agreement with the experimental data, CADY is a polymorphic peptide partly helical. Taking into consideration the polymorphism of CADY, we calculated and compared several complexes with peptide/siRNA ratios of up to 40. Four complexes were run by using molecular dynamics. The initial binding of CADYs is essentially due to the electrostatic interactions of the arginines with siRNA phosphates. Due to a repetitive arginine motif (XLWR(K)) in CADY and to the numerous phosphate moieties in the siRNA, CADYs can adopt multiple positions at the siRNA surface leading to numerous possibilities of complexes. Nevertheless, several complex properties are common: an average of 14+/-1 CADYs is required to saturate a siRNA as compared to the 12+/-2 CADYs experimentally described. The 40 CADYs/siRNA that is the optimal ratio for vector stability always corresponds to two layers of CADYs per siRNA. When siRNA is covered by the first layer of CADYs, the peptides still bind despite the electrostatic repulsion. The peptide cage is stabilized by hydrophobic CADY-CADY contacts thanks to CADY polymorphism. The analysis demonstrates that the hydrophobicity, the presence of several positive charges and the disorder of CADY are mandatory to make stable the CADY-siRNA complexes.
http://hdl.handle.net/2268/134944
Copyright (c) 2012 Elsevier B.V. All rights reserved.

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
299.pdfAuthor preprint1.67 MBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.