Selenium Atom-Specific Mutagenesis (SAM) for Crystallography, DNA Nanostructure Design, and Other Applications - DNA Nanotechnology: From Structure to Function - page 49

corresponding native DNA did not show any conductivity. This study demonstrates
the potential of the Te-DNA in material science, such as nanotechnology and
nanoelectronic device design.

3.6 Perspective

In this chapter, we provide a brief introduction of current research progress of
SeNA as well as other chalcogen-modified nucleic acids. The unique properties of
these chalcogen elements offer potential usefulness in many nucleic acid research
areas, including X-ray crystallography, drug discovery, disease diagnosis, enzyme
mechanistic study, and material sciences . In the attempt to understand the structures
of nucleic acid nano-assemblies, 2D lattices constructed by modified nucleic
acids could be characterized by atomic force microscopy (AFM), transmission
electron microscopy (TEM), and scanning tunneling microscope (STM). For more
detailed 3D structures of nucleic acid architectures, X-ray crystallographic study is
necessary. Obtaining crystals and solving the phasing problem are the most critical
steps in nucleic acid crystallography. Again, the selenium derivatization can greatly
facilitate this process by accelerating high-quality crystal growth and providing
phase information.
Furthermore, via solid-phase DNA/RNA synthesis, the atom-specifically mod-
ified phosphoramidite building blocks bring many diversified functionalities into
oligonucleotides without causing significant perturbation on overall structures. The
new generation of the Se modifications is currently under development. We are
confident that the novel Se modifications will tremendously facilitate structure-
and-function studies of nucleic acids and their protein complexes in the future.
It is expected that via the atom-specific S, Se, and/or Te modifications and
more chemistry development, various functionalities can be used to create the
functional oligonucleotides. These functions include the tailor-made base pairing
and stacking, colored DNA and RNA, reduced molecular dynamics, conformation-
controlled sugar pucker, molecular imaging, and conductivity. The atom-specific
functionalization allows designing and building highly functionalized nucleic acid
nano-structures and nano-devices in well-controlled and predictable manners. We
are confident that the atom-specifically modified nucleic acids, especially SeNA
via SAM, will significantly contribute to the rapid advancement of nucleic acid
nanotechnology.

Acknowledgment This work was financially supported by the Georgia Cancer Coalition (GCC)
Distinguished Cancer Clinicians and Scientists and NIH (NIGMS-R01GM095881).