In the rapid and fast-growing world of nanotechnology, researchers are
continually on the lookout for new building blocks to push innovation
and discovery to scales much smaller than the tiniest speck of dust.
In the Biodesign Institute at Arizona State University, researchers
are using DNA to make intricate nano-sized objects. Working at this
scale holds great potential for advancing medical and electronic
applications. DNA, often thought of as the molecule of life, is an
ideal building block for nanotechnology because they self-assemble,
snapping together into shapes based on natural chemical rules of
attraction. This is a major advantage for Biodesign researchers like
Hao Yan, who rely on the unique chemical and physical properties of DNA
to make their complex nanostructures.
While scientists are fully exploring the promise of DNA
nanotechnology, Biodesign Institute colleague John Chaput is working to
give researchers brand new materials to aid their designs. In an
article recently published in the Journal of the American Chemical
Society, Chaput and his research team have made the first
self-assembled nanostructures composed entirely of glycerol nucleic
acid (GNA)–a synthetic analog of DNA.
"Everyone in DNA nanotechnology is essentially limited by what they
can buy off the shelf," said Chaput, who is also an ASU assistant
professor in the Department of Chemistry and Biochemistry. "We wanted
to build synthetic molecules that assembled like DNA, but had
additional properties not found in natural DNA."
The DNA helix is made up of just three simple parts: a sugar and a
phosphate molecule that form the backbone of the DNA ladder, and one of
four nitrogenous bases that make up the rungs. The nitrogenous base
pairing rules in the DNA chemical alphabet fold DNA into a variety of
useful shapes for nanotechnology, given that "A" can only form a
zipper-like chemical bond with "T" and "G" only pair with "C."
In the case of GNA, the sugar is the only difference with DNA. The
five carbon sugar commonly found in DNA, called deoxyribose, is
substituted by glycerol, which contains just three carbon atoms.
Chaput has had a long-standing interest in tinkering with chemical
building blocks used to make molecules like proteins and nucleic acids
that do not exist in nature. When it came time to synthesize the first
self-assembled GNA nanostructures, Chaput had to go back to basics.
"The idea behind the research was what to start with a simple DNA
nanostructure that we could just mimic."
The first self-assembled DNA nanostructure was made by Ned Seeman’s
lab at Columbia University in 1998, the very same laboratory where ASU
professor Hao Yan received his Ph.D. Chaput’s team, which includes
graduate students Richard Zhang and Elizabeth McCullum were not only
able to duplicate these structures, but, unique to GNA, found they
could make mirror image nanostructures.
In nature, many molecules important to life like DNA and proteins
have evolved to exist only as right-handed. The GNA structures, unlike
DNA, turned out to be ‘enantiomeric’ molecules, which in chemical terms
means both left and right-handed.
"Making GNA is not tricky, it’s just three steps, and with three
carbon atoms, only one stereo center," said Chaput. "It allows us to
make these right and left-handed biomolecules. People have actually
made left-handed DNA, but it is a synthetic nightmare. To use it for
DNA nanotechnology could never work. It’s too high of a cost to make,
so one could never get enough material."
The ability to make mirror image structures opens up new
possibilities for making nanostructures. The research team also found a
number of physical and chemical properties that were unique to GNA,
including having a higher tolerance to heat than DNA nanostructures.
Now, with a new material in hand, which Chaput dubs ‘unnatural nucleic
acid nanostructures,’ the group hopes to explore the limits on the
topology and types of structure they can make.
"We think we can take this as a basic building block and begin to
build more elaborate structures in 2-D and see them in atomic force
microscopy images," said Chaput. "I think it will be interesting to see
where it will all go. Researchers come up with all of these clever
Arizona State University. April 2008.