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(Figure 10.3b). Terminal modification of nucleic acid oligomers with ligands was used to
create a broad range of structures, including metal-containing, single strands, hairpins,
duplexes, and triplexes (Figure 10.3c, d). Within these hybrid inorganic-nucleic acid
structures, there are synergetic relationships between: (a) metal coordination and oligo-
nucleotide hybridization, and (b) the properties of the metal complexes and those of the
nucleic acid that form the hybrid inorganic-nucleic acid ensemble. For example, upon
hybridization of ligand-modified oligonucleotides to form a duplex that contains ligands
in complementary positions, the binding constant for a metal ion to the ligands brought in
close proximity of each other by the duplex is generally larger than that to the same free
ligand [12b,16c]. Conversely, ligand-modified oligonucleotides that may form two alter-
nate structures such as a duplex or a hairpin (e.g., Figure 10.3b) will adopt preferably one
of these two structures in which the metal ion has its most common coordination number
and geometry [19].
10.2 Brief Overview of Synthetic Analogues of DNA: PNA, LNA, UNA, and
GNA
Metal-based alternative base pairs have been incorporated to date in DNA, RNA, and sev-
eral of their synthetic analogues, including peptide nucleic acid (PNA), locked nucleic
acid (LNA), unlocked nucleic acid (UNA), and glycol nucleic acid (GNA). These ana-
logues can form duplexes by Watson-Crick base pairing with DNA and RNA, and thus
have potential for antisense and antigene applications. Their backbones are different from
that of DNA, which makes them chemically and biochemically more stable than DNA,
and thus more appropriate in certain nanotechnology and biology applications.
PNA, which was discovered in 1991, has a pseudo-peptide backbone originally based
on N-(2-aminoethylglycine) (Aeg), which is neutral and achiral (Figure 10.4) [20]. The
thermal stability of PNA
DNA
duplexes because the backbone is neutral. Hence, mismatches and in general chemical
modifications that affect the base pairing, have a larger effect on the thermal stability of
PNA duplexes is higher than that of PNA
DNA or DNA
Figure 10.4 Chemical structure of single strands of DNA, PNA, LNA, and GNA.
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