correlated physical parameters, so that the distance is shortest when the angle
approaches the ideality, namely, 180
. Therefore, the shortest distance produces
the strongest hydrogen bonds.
The formation of such a bond is easier between soluble distinct molecules, or
between a soluble entity and a grafted one, compared to intramolecular functional
sites. In this respect, the formation of hydrogen bonds between grafted aptamers and
free proteins is considered favorable. Such a hydrogen bonding formation is also
observed with aromatic structures, where the global electronegativity originates from
π-orbitals. Quite recently, it has been reported that DNA-protein π-π interactions
contribute to different aspects of noncovalent interactions between both cyclic and
acyclic π-containing components, with a significant contribution to the stability of
DNA-protein complexes in nature [83].
Aptamers comprise regions with paired nucleotides and others with unpaired
bases (see Sect. 3.2 above). Interactions between proteins and nucleic acids, involving hydrogen bondings, essentially involve unpaired nucleotides as described
[84]. Frequently involved biochemical structures are arginine and asparagine
residues, both able to interact with uracile, while lysine and threonine interact with
adenine. Glutamic acid forms stable complexes with guanine. However, since
arginine and lysine show more electronegative atoms compared to other amino
acids, they are more frequently involved in hydrogen bonds. In another investigation, Nobeli et al. [85] indicated that tyrosine and threonine interact preferably with
adenine and guanine, respectively, but glutamic acid and aspartic acid interact
mostly with guanine and adenine. As shown, it appeared that the amino acids
contribute to the formation of more than 70% of hydrogen bonds and the remaining
less than 30% are formed with the main protein chain, where coplanar peptide
groups (–NH–CO–) are regularly disseminated all along the polypeptide chain,
and are at the basis of the formation of beta-sheets and alpha-helix structures
[86]. Concerning the propensity of unpaired nucleotides to form hydrogen bondings
with proteins, uracile appeared to be the primary structure. L-sheet residues in
proteins have a high tendency to recognize the unpaired nucleotides, especially
adenine, while cytosine tends to interact with helix structures of proteins.
Since hydrogen bonds involve mostly the exposed side chain of amino acids of
the protein, it is interesting to notice that their protonation state depends on environmental pH, explaining the dependency of some hydrogen bonding on the
pH. This is an important point, because it allows conceptualizing the mechanisms
of association and dissociation of proteins from the grafted aptamer during practical
applications and particularly the elution phase. To complete this section, it should be
underlined that no hydrogen bonds have been reported with side chains of hydrophobic amino acids.
3.3.3 Hydrophobic Associations
Hydrophobic associations are noncovalent exothermic processes between nonpolar
molecules in aqueous environments. In water, these hydrophobic associations are
104
G. Perret and E. Boschetti
approaches the ideality, namely, 180
. Therefore, the shortest distance produces
the strongest hydrogen bonds.
The formation of such a bond is easier between soluble distinct molecules, or
between a soluble entity and a grafted one, compared to intramolecular functional
sites. In this respect, the formation of hydrogen bonds between grafted aptamers and
free proteins is considered favorable. Such a hydrogen bonding formation is also
observed with aromatic structures, where the global electronegativity originates from
π-orbitals. Quite recently, it has been reported that DNA-protein π-π interactions
contribute to different aspects of noncovalent interactions between both cyclic and
acyclic π-containing components, with a significant contribution to the stability of
DNA-protein complexes in nature [83].
Aptamers comprise regions with paired nucleotides and others with unpaired
bases (see Sect. 3.2 above). Interactions between proteins and nucleic acids, involving hydrogen bondings, essentially involve unpaired nucleotides as described
[84]. Frequently involved biochemical structures are arginine and asparagine
residues, both able to interact with uracile, while lysine and threonine interact with
adenine. Glutamic acid forms stable complexes with guanine. However, since
arginine and lysine show more electronegative atoms compared to other amino
acids, they are more frequently involved in hydrogen bonds. In another investigation, Nobeli et al. [85] indicated that tyrosine and threonine interact preferably with
adenine and guanine, respectively, but glutamic acid and aspartic acid interact
mostly with guanine and adenine. As shown, it appeared that the amino acids
contribute to the formation of more than 70% of hydrogen bonds and the remaining
less than 30% are formed with the main protein chain, where coplanar peptide
groups (–NH–CO–) are regularly disseminated all along the polypeptide chain,
and are at the basis of the formation of beta-sheets and alpha-helix structures
[86]. Concerning the propensity of unpaired nucleotides to form hydrogen bondings
with proteins, uracile appeared to be the primary structure. L-sheet residues in
proteins have a high tendency to recognize the unpaired nucleotides, especially
adenine, while cytosine tends to interact with helix structures of proteins.
Since hydrogen bonds involve mostly the exposed side chain of amino acids of
the protein, it is interesting to notice that their protonation state depends on environmental pH, explaining the dependency of some hydrogen bonding on the
pH. This is an important point, because it allows conceptualizing the mechanisms
of association and dissociation of proteins from the grafted aptamer during practical
applications and particularly the elution phase. To complete this section, it should be
underlined that no hydrogen bonds have been reported with side chains of hydrophobic amino acids.
3.3.3 Hydrophobic Associations
Hydrophobic associations are noncovalent exothermic processes between nonpolar
molecules in aqueous environments. In water, these hydrophobic associations are
104
G. Perret and E. Boschetti