The authors suggested that when the alpha-helix CPP is tilted, it can fit into the major groove of the dsRNA via hydrogen bonds and van der Waals interactions [27-29].
When inspecting the orientation and placement of the cationic CPP on the siRNA (in both A- and B-forms), in all considered cases the initial CPP complexation occurs at the major groove of the siRNA (see Figures 5A1 and 5B1).
Initially the hydrophobic peptides were predicted to bind to either the major groove or the minor groove.
(1) Initially electrostatic and shape complementarity drive the binding of cell penetrating peptides into the major groove of siRNA, where the maximum salt bridges may be formed.
The main reason that can be identified is the shape of the major groove of siRNA.
Sundaralingam, "Protein-nucleic acid interaction: major groove recognition determinants," in Encyclopedia of Life Sciences, John Wiley & Sons Ltd, Chichester, UK, 2001.
The compound [Fe2L3]4+ is an iron triple helicate with three organic strands wrapped around two iron centres to give a helix which looks cylindrical in shape and neatly fits within the major groove of a DNA helix.
The high positive charge of the compound enhances its ability to bind to DNA, which is negatively charged, and when the iron-helicate binds to the major groove of DNA, it coils the DNA so that it is no longer available to bind to anything else and is not able to drive biological or chemical processes.
