Selenium Atom-Specific Mutagenesis (SAM) for Crystallography, DNA Nanostructure Design, and Other Applications - DNA Nanotechnology: From Structure to Function - page 28

functions of the fundamental building block of life. Today, nucleic acids are not only
just important to molecular biology and genetics but also to novel drug discovery,
as well as material sciences, such as nucleic acid nanotechnology.
Nanoscience has emerged as a new field for three decades. It is highly diversified
and involves many disciplines, including physics (such as surface science and
semiconductor manufacturing), chemistry (such as organic chemistry, biochemistry,
and analytical chemistry), as well as molecular biology. In nanotechnology, nucleic
acids serve as engineered building blocks rather than genetic information carriers.
The hydrophobic nucleobases, hydrophilic sugar, backbone, and base pairs enable
controlled assembly of the complex structures, such as duplexes, triplexes, quadru-
plexes, knots, Holliday junctions, and other structure motifs. These properties of the
predictable and well-behaving nucleic acids allow rational design of complicated
DNA and RNA nano-architectures. A nanoscale nucleic acid structure could be
built up by designing nucleic acids with different sizes and sequences paired with
complementary strands, in order to assemble into specially designed shapes and
geometries. However, the rapid advancement of nucleic acid nanotechnology has
also faced many new challenges, especially novel functionalities, such as high
conductivity and useful spectroscopy property, which four natural nucleotides
(or nucleobases) can no long offer. In order to obtain functionally diversified
nucleic acids as nanomaterials, nucleotide analogs with various modifications and
functionalities are highly desired, as long as the structures and functions are still
predictable after the modifications.
Currently, the advances in the designed oligonucleotide synthesis have allowed
chemists to synthesize virtually any nucleoside analogs and incorporate them
into oligonucleotides by solid-phase strategy [ 2 , 3 ]. Over the past two decades,
mainly driven by continuous effort in searching for antisense [ 4 - 9 ]andsiRNA
oligonucleotides [ 10 - 14 ] as well as the fast development in related synthetic
methodologies, a broad collection of site-specific labeling methods is available
nowadays. For seeking useful functionalities while preserving the structure-and-
function predictability in the nucleic acid nanotechnology, the atom-specific modifi-
cations (such as F and S replacements) are very promising strategies, which provide
various functionalities and preserve the original structure and structure-and-function
predictability. Moreover, since oxygen, sulfur, selenium, and tellurium are in the
same elemental family, replacing oxygen atoms with other chalcogen atoms will
not cause significant changes in the local conformations let alone overall structures,
which preserves the nucleic acid structures in a predictable manner. Furthermore, the
valuable differences in chemical and electronic properties enable various functions
and applications, including phasing, crystallization, and high-resolution structure
determination in X-ray crystallography [ 15 , 16 ], base-pair high fidelity [ 17 , 18 ],
conformation restriction [ 19 ], redox property [ 20 , 21 ], site-specific self-cleavage
[ 21 ], as well as molecular assembly and imaging [ 22 , 23 ].
In this chapter, we will give a brief introduction of the development and functions
of chalcogen-modified nucleic acids, particularly selenium-modified nucleic acids