surrounding the molecule. Any variation in the ionic context could have a strong
effect on RNA stability and consequently on its biological functionality. Differently
from DNA, RNA molecules can have a natural catalytic activity, a valuable feature
in the perspective to design a nucleic acid bioreceptor.
Another relevant characteristics of RNAs that should be considered is their
higher sensitivity to chemical changes than DNA, actually hundred different RNA
modifications are known [18]. This large number of variations gives strong indication that RNAs are highly configurable molecule. The design of biosensors based
on functionalized nucleic acids have to take some key points into account.: (1) sequence heterogeneity; (2) hierarchical conformational organization; (3) component
modularity; (4) selectivity stereochemical interactions; (5) cooperative effects (long
range interactions) derived from folding [19]. The design of a RNA probe, taking its
flexibility into account, have to minimize the number of metastable folded structures. The development of nucleic-acid based biosensor has been initially focused
on the use of DNA. DNA can take different duplex conformations: A-DNA,
B-DNA and Z-DNA; these conformation can be converted from one to by the effect
of external factors [20, 21]. The identification of local structural elements is one of
the reason for biosensor and nanotechnological application of Nucleic acids [22,
23]. Nucleic acids are, from a chemical-physics perspective, a class of natural
foldamers. A foldamer is, from the chemical-physics point of view, a natural or
synthetic polymer capable to originate, in solution, an ordered 3D structure [24]
having well defined self-assembly, recognition and catalytic properties.
Among the different possible folding conformation originated by a nucleic acids
[25] some of them have a relevance for biosensors applications: 3-way (3WJ) and
4-way (4WJ) junctions, G-quadruplex, hairpin, stem-loop, pseudoknot and triple
helix (TFO). The junctions requires three o more DNA or RNA helices originating
a branched conformations. The 3WJ requires three helices, linked together by a
connection element, with one high flexibility helix. The 4-way junction (4WJ)
(Hollyday-junction) is formed by four dsDNA joined together; these conformation
are transient high order branched structure occurring during specific cellular processes. 3WJ and 4WJ structure have been also identified in RNAs [25] (Fig. 1).
Another important structural motif is the G-quadruplex, related with the presence
of G-rich domains (Fig. 2) The G-quadruplex is the results of interaction between
coplanar arrays of guanine called G-tetrads; they can occur on a single strand
(intramolecular) or between two strands (intermolecular) DNA and RNA
G-quadruplexes are capable to form, by charge transfer between donor and
acceptor, an internal space [26, 27] in which ionic displacement depend on the
specific ion affinity for the nucleic acid. The biological function of DNA and RNA
G-quadruplexes is different; the DNA G-quadruplexes seem to be involved in
maintenance of genomic integrity and transcriptional processes. RNA
G-quadruplexes seem to be implied in several different biological activities. such as
transcription termination, pre-mrna splicing and mRNA targeting [28] (Fig. 2).
High target specificity is the foremost feature of a nucleic acid-based biosensor;
it is strongly correlate with the structure of sensing element that have to recognize
the analyte.
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P. Arrigo and D. Baroni
effect on RNA stability and consequently on its biological functionality. Differently
from DNA, RNA molecules can have a natural catalytic activity, a valuable feature
in the perspective to design a nucleic acid bioreceptor.
Another relevant characteristics of RNAs that should be considered is their
higher sensitivity to chemical changes than DNA, actually hundred different RNA
modifications are known [18]. This large number of variations gives strong indication that RNAs are highly configurable molecule. The design of biosensors based
on functionalized nucleic acids have to take some key points into account.: (1) sequence heterogeneity; (2) hierarchical conformational organization; (3) component
modularity; (4) selectivity stereochemical interactions; (5) cooperative effects (long
range interactions) derived from folding [19]. The design of a RNA probe, taking its
flexibility into account, have to minimize the number of metastable folded structures. The development of nucleic-acid based biosensor has been initially focused
on the use of DNA. DNA can take different duplex conformations: A-DNA,
B-DNA and Z-DNA; these conformation can be converted from one to by the effect
of external factors [20, 21]. The identification of local structural elements is one of
the reason for biosensor and nanotechnological application of Nucleic acids [22,
23]. Nucleic acids are, from a chemical-physics perspective, a class of natural
foldamers. A foldamer is, from the chemical-physics point of view, a natural or
synthetic polymer capable to originate, in solution, an ordered 3D structure [24]
having well defined self-assembly, recognition and catalytic properties.
Among the different possible folding conformation originated by a nucleic acids
[25] some of them have a relevance for biosensors applications: 3-way (3WJ) and
4-way (4WJ) junctions, G-quadruplex, hairpin, stem-loop, pseudoknot and triple
helix (TFO). The junctions requires three o more DNA or RNA helices originating
a branched conformations. The 3WJ requires three helices, linked together by a
connection element, with one high flexibility helix. The 4-way junction (4WJ)
(Hollyday-junction) is formed by four dsDNA joined together; these conformation
are transient high order branched structure occurring during specific cellular processes. 3WJ and 4WJ structure have been also identified in RNAs [25] (Fig. 1).
Another important structural motif is the G-quadruplex, related with the presence
of G-rich domains (Fig. 2) The G-quadruplex is the results of interaction between
coplanar arrays of guanine called G-tetrads; they can occur on a single strand
(intramolecular) or between two strands (intermolecular) DNA and RNA
G-quadruplexes are capable to form, by charge transfer between donor and
acceptor, an internal space [26, 27] in which ionic displacement depend on the
specific ion affinity for the nucleic acid. The biological function of DNA and RNA
G-quadruplexes is different; the DNA G-quadruplexes seem to be involved in
maintenance of genomic integrity and transcriptional processes. RNA
G-quadruplexes seem to be implied in several different biological activities. such as
transcription termination, pre-mrna splicing and mRNA targeting [28] (Fig. 2).
High target specificity is the foremost feature of a nucleic acid-based biosensor;
it is strongly correlate with the structure of sensing element that have to recognize
the analyte.
218
P. Arrigo and D. Baroni