medium length, for instance, several dozens of nucleotides. Interestingly, this is
the case for aptamer ligands used in affinity chromatography, where the exact
sequence may not be sufficient to understand the tertiary structure stability of
these ligands. Nevertheless, the prediction of secondary and tertiary configurations
is still inaccurate from medium to large aptamers (e.g., sequences longer than
100 nucleotides) [76].
3.3 Aptamer-Protein Interaction
Literature related to aptamer-protein interactions in affinity chromatography is
almost nonexistent. A RNA or DNA sequence is not a simple linear primary
structure, but, as mentioned above, a macromolecule subject to secondary and
tertiary configurations [69, 77] (see also Sect. 3.2).
It is the tertiary structure of the aptamer ligands that defines the specificity for
target proteins. Modifications of this structure can cause the reduction of affinity
between partner macromolecules up to the point of the complete annihilation of the
interaction.
The interaction between proteins and aptamers develops thanks to several concurrent elementary interactions. For instance, in proteins, secondary amide bonds
between amino acids constituting the peptide chain contribute to hydrogen bonding.
The side chain groups of amino acids are also particularly active to develop a variety
of interaction phenomena in terms of diversity and strength. It is therefore essential
that all the internal molecular interactions, responsible for the spatial configuration
of the target protein, remain intact all along the recognition phase with the aptamer.
Bonds between the grafted aptamer and its protein target are individually considered as weak interactions that are at least one order of magnitude less strong than
covalent bonds. They can be grouped into ion-ion, hydrogen bonding, hydrophobic
associations, and dipole-dipole, these being generally grouped under the name van
der Waals interactions. Taken together, all these molecular interactions describe how
atoms or groups of atoms are attracted or repelled to each other, to minimize the
energy of conformation of the complex [78, 79].
The involvement of atoms or groups of atoms in a cooperative manner is, in
general, distance-dependent, with the energies being inversely proportional to the
distance separating the two groups. Opposed to attraction from two entities are the
repulsion effects that originate from electrostatic implications when the electrical
charges are of the same sign, as well as steric repulsions which do not allow two
atoms to occupy the same space at the same time. While the electrostatic repulsion
acts at a quite long distance, steric repulsion occurs at very short distances. Together,
attractive and repulsive exclusion interactions define an optimum distance separating
any two entities, at which the energy is minimized.
To try explaining the specificity of interaction between a grafted aptamer and its
corresponding affinity protein, we consider three main interaction forces that are
present most of the time, namely, electrostatic interactions, hydrogen bonding, and
102
G. Perret and E. Boschetti
the case for aptamer ligands used in affinity chromatography, where the exact
sequence may not be sufficient to understand the tertiary structure stability of
these ligands. Nevertheless, the prediction of secondary and tertiary configurations
is still inaccurate from medium to large aptamers (e.g., sequences longer than
100 nucleotides) [76].
3.3 Aptamer-Protein Interaction
Literature related to aptamer-protein interactions in affinity chromatography is
almost nonexistent. A RNA or DNA sequence is not a simple linear primary
structure, but, as mentioned above, a macromolecule subject to secondary and
tertiary configurations [69, 77] (see also Sect. 3.2).
It is the tertiary structure of the aptamer ligands that defines the specificity for
target proteins. Modifications of this structure can cause the reduction of affinity
between partner macromolecules up to the point of the complete annihilation of the
interaction.
The interaction between proteins and aptamers develops thanks to several concurrent elementary interactions. For instance, in proteins, secondary amide bonds
between amino acids constituting the peptide chain contribute to hydrogen bonding.
The side chain groups of amino acids are also particularly active to develop a variety
of interaction phenomena in terms of diversity and strength. It is therefore essential
that all the internal molecular interactions, responsible for the spatial configuration
of the target protein, remain intact all along the recognition phase with the aptamer.
Bonds between the grafted aptamer and its protein target are individually considered as weak interactions that are at least one order of magnitude less strong than
covalent bonds. They can be grouped into ion-ion, hydrogen bonding, hydrophobic
associations, and dipole-dipole, these being generally grouped under the name van
der Waals interactions. Taken together, all these molecular interactions describe how
atoms or groups of atoms are attracted or repelled to each other, to minimize the
energy of conformation of the complex [78, 79].
The involvement of atoms or groups of atoms in a cooperative manner is, in
general, distance-dependent, with the energies being inversely proportional to the
distance separating the two groups. Opposed to attraction from two entities are the
repulsion effects that originate from electrostatic implications when the electrical
charges are of the same sign, as well as steric repulsions which do not allow two
atoms to occupy the same space at the same time. While the electrostatic repulsion
acts at a quite long distance, steric repulsion occurs at very short distances. Together,
attractive and repulsive exclusion interactions define an optimum distance separating
any two entities, at which the energy is minimized.
To try explaining the specificity of interaction between a grafted aptamer and its
corresponding affinity protein, we consider three main interaction forces that are
present most of the time, namely, electrostatic interactions, hydrogen bonding, and
102
G. Perret and E. Boschetti