Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists reinvent DNA as template to produce organic molecules

20.08.2004


New technique, reported in Science, unites organic fragments by piggybacking on DNA strands



By piggybacking small organic molecules onto short strands of DNA, chemists at Harvard University have developed an innovative new method of using DNA as a blueprint not for proteins but for collections of complex synthetic molecules. The researchers will report on the prolific technique, dubbed "DNA-templated library synthesis," this week on the web site of the journal Science.

"The basic structures of proteins and nucleic acids seem limited when compared with the structures that can be created using modern synthetic chemistry, and yet this very modest set of protein and nucleic acid building blocks has given rise to the incredible complexity and diversity of living systems," says David R. Liu, associate professor of chemistry and chemical biology at Harvard. "We’re interested in marrying fundamental features of biomolecules with synthetic organic chemistry in order to apply techniques such as translation, selection, and amplification to molecules beyond those found in cells and organisms."


Liu and his colleagues attached organic molecules to single DNA strands, each containing 10 DNA bases (A, C, G, or T). When two DNA strands with complementary sequences (A matches T, G matches C) spontaneously bond together, their associated organic molecules undergo a chemical reaction to generate a product. As a result, the DNA strands essentially serve as a miniature, sequence-programmable assembly line for products of chemical synthesis.

Because the resulting synthetic compounds are linked to DNA, techniques long used to screen and amplify the genetic mainstay can now be applied. Molecules can be "selected" for desired functional properties, and the survivors of these selections can then be copied using the polymerase chain reaction (PCR).

The application of DNA-templated synthesis has enabled a collection of DNA strands to be transformed into a corresponding collection of sequence-programmed small macrocyclic molecules with potentially interesting chemical and biological properties. A single member of the collection survived a selection on the basis of its ability to bind to a protein target, and the DNA encoding the survivor was amplified by PCR and sequenced to reveal its identity.

Liu’s team found that small molecules bound to DNA can react to form larger products even when the DNA bases used to zip together the small molecules are far apart on a DNA template. This means that a template strand of 30 DNA bases, complementary to Liu’s DNA codes for three different organic molecules, can encode three separate chemical reactions, leading to the multistep DNA-programmed synthesis of relatively complex cyclic products.

Chemical synthesis occurs very differently in laboratories and in cells. Chemists typically work with molecules that react to form products when they randomly collide at high concentrations. By contrast, biomolecules are found within cells at concentrations that are often a million times lower than the concentrations of molecules in laboratory reactors. In nature, the reactions between these highly dilute molecules are directed by enzymes that selectively bring certain biological reactants together. Liu and his colleagues are now using DNA as a similar type of intermediary to bring together synthetic small molecules that are otherwise too dilute to react, allowing minute quantities of sparse molecules to behave as denser mixtures when assembled together by DNA base pairing.

"We recognized that in order to apply such an approach to as many synthetic molecules as possible, we’d have to use a different type of template than an enzyme," Liu says. "The natural and robust zipping up of complementary DNA strands is a simple way to bring molecules at low concentrations together without having to develop an entirely new class of enzymes for each different type of molecule."

The 10-base DNA strands used by Liu’s team are large enough to be stable at room temperature and in theory can encode thousands of individual small organic molecules.

Liu’s co-authors are Zev J. Gartner, Brian N. Tse, Rozalina Grubina, Jeffrey B. Doyon, and Thomas M. Snyder, all of Harvard’s Department of Chemistry and Chemical Biology. Their work was funded by the National Institute of General Medical Sciences at the National Institutes of Health, the Office of Naval Research, the Arnold and Mabel Beckman Foundation, the Searle Scholars Foundation, the Alfred P. Sloan Foundation, and fellowships from Bristol-Myers Squibb and the National Science Foundation.

Steve Bradt | EurekAlert!
Further information:
http://www.harvard.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>