The hot action in many areas of technology revolves around how to make things smaller and smaller. Bucking this trend, scientists at Stanford University have synthesized an artificial DNA strand with molecules about 15 percent larger than the natural variety. This so-called xDNA has properties lacking in the puny DNA that nature cooks up. It is more stable, for example. It also glows under ultraviolet light. These traits suggest that xDNA could be useful in genetic diagnostic procedures and, potentially, artificial forms of life. “Our biggest interest is whether we can design our own genetic system,” says chemistry professor Eric Kool, who led the Stanford research team. “I think we’re well on our way.”What makes xDNA different from regular DNA is its structure. Normally, DNA is a string of nucleotides, each of which comprises a sugar, a phosphate, and a base: either adenine, thymine, guanine, or cytosine (represented in DNA descriptions as A, T, G, and C). When DNA strands bond with one another, the bases match up in a particular way: adenine always bonds with thymine, and guanine with cytosine.
About thirty years ago, Nelson Leonard, then a University of Illinois chemist and now at the California Institute of Technology, found a way to stretch adenine so that it would fluoresce when exposed to ultraviolet light. What Leonard couldn’t do was attach the sugar and phosphate to the base, making a complete nucleotide; scientists at the time didn’t know how to make DNA, though now the process of creating artificial strands is commonly used in genetic medical diagnostics.
What Kool sought was a way of making a DNA double helix. First he synthesized two expanded bases: adenine and thymine (xA and xT). He then made nucleotides out of the xA and xT bases with appropriate sugars and phosphates. By pairing an xA with a normal T and an xT with a normal A, Kool was able to assemble them into a double helix just wide enough to contain the stretched bases.
Building the nucleotides took four years of work. Kool started by designing the structure of the stretched bases, then moved to synthesis, which required finding appropriate forms of sugars and phosphates. “We did chemical reaction after chemical reaction after chemical reaction,” Kool says. Purification of the results can take days, or even weeks. And because such synthesis hadn’t been done before, there were many dead ends.