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 Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>