and contains approximatively 147 bp of DNA wrapped in roughly two superhelical
turns around an octamer of four core histones (H2A, H2B, H3, H4) (Scheme 3b): the
DNA that links two neighboring nucleosomes is called linker DNA (55 bp) [40]. The
structure adopts a “beads-on-a-string” configuration (Scheme 3c).
The H1 protein interacts with NCPs and organizes linker DNA, helping stabilize the
zig-zagged 30 nm chromatin fiber. This is a nice example found in Nature of controlled
complexation of genetic material [negatively charged DNA and histones, constituted
mainly of positively charged amino acids such as arginine (Arg) and lysine (Lys)].
The selective binding of a protein to a particular DNA sequence requires the
recognition by the protein of an ensemble of steric and chemical features that
delineate the binding site [41]. DNA–protein recognition occurs very often by
insertion of an R-helix into the major groove of dsDNA. A specific DNA sequence
is then recognized through:
1. Formation of extensive hydrogen bonding and van der Waals interactions with
the bases (“direct readout”)
2. Recognition of sequence-dependent conformational features through electrostatic interactions with the negatively charged phosphodiester backbone (“indirect readout”)
The structure of these DNA-binding proteins and the way they bind to DNA can be
taken as inspiration for the rational design of synthetic polymers as DNA complexants.
1.2 Polyelectrolytes
Due to the presence of negatively charged phosphate groups, DNA is a strong
polyanion and can forms complexes with positively charged polymers. DNA is
usually defined by its number of base pairs and molecular weight (in Daltons) per
charge (two charges per bp, ~650 Da/bp). It is important to mention that the
polyelectrolyte character of DNA largely controls its behavior in solution.
1.2.1 Weak and Strong Polyelectrolytes
Polyelectrolytes are polymers whose repeating units bear an ionizable group. These
groups will dissociate in aqueous solutions, making the polymers charged.
Polyelectrolytes can be divided into weak and strong polyelectrolytes. Strong
polyelectrolytes dissociate completely in solution for most reasonable pH values,
whereas weak polyelectrolytes have a dissociation constant (pK a ) in the range of
~2 to 10, meaning that they will be partially dissociated at intermediate pH.
In the case of strong polyelectrolytes, the number and position of charges is
fixed; variation of pH or ion concentration will not affect the number of charges. On
the other hand, weak polyelectrolytes are not fully charged in solution, and their
average degree of charges is given by the dissociation–association equilibrium
110
A. Bertin
turns around an octamer of four core histones (H2A, H2B, H3, H4) (Scheme 3b): the
DNA that links two neighboring nucleosomes is called linker DNA (55 bp) [40]. The
structure adopts a “beads-on-a-string” configuration (Scheme 3c).
The H1 protein interacts with NCPs and organizes linker DNA, helping stabilize the
zig-zagged 30 nm chromatin fiber. This is a nice example found in Nature of controlled
complexation of genetic material [negatively charged DNA and histones, constituted
mainly of positively charged amino acids such as arginine (Arg) and lysine (Lys)].
The selective binding of a protein to a particular DNA sequence requires the
recognition by the protein of an ensemble of steric and chemical features that
delineate the binding site [41]. DNA–protein recognition occurs very often by
insertion of an R-helix into the major groove of dsDNA. A specific DNA sequence
is then recognized through:
1. Formation of extensive hydrogen bonding and van der Waals interactions with
the bases (“direct readout”)
2. Recognition of sequence-dependent conformational features through electrostatic interactions with the negatively charged phosphodiester backbone (“indirect readout”)
The structure of these DNA-binding proteins and the way they bind to DNA can be
taken as inspiration for the rational design of synthetic polymers as DNA complexants.
1.2 Polyelectrolytes
Due to the presence of negatively charged phosphate groups, DNA is a strong
polyanion and can forms complexes with positively charged polymers. DNA is
usually defined by its number of base pairs and molecular weight (in Daltons) per
charge (two charges per bp, ~650 Da/bp). It is important to mention that the
polyelectrolyte character of DNA largely controls its behavior in solution.
1.2.1 Weak and Strong Polyelectrolytes
Polyelectrolytes are polymers whose repeating units bear an ionizable group. These
groups will dissociate in aqueous solutions, making the polymers charged.
Polyelectrolytes can be divided into weak and strong polyelectrolytes. Strong
polyelectrolytes dissociate completely in solution for most reasonable pH values,
whereas weak polyelectrolytes have a dissociation constant (pK a ) in the range of
~2 to 10, meaning that they will be partially dissociated at intermediate pH.
In the case of strong polyelectrolytes, the number and position of charges is
fixed; variation of pH or ion concentration will not affect the number of charges. On
the other hand, weak polyelectrolytes are not fully charged in solution, and their
average degree of charges is given by the dissociation–association equilibrium
110
A. Bertin