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."