Using metal atoms as molecular matchmakers, University of Rochester chemist Benjamin Miller has devised a new way of forming a nearly endless variety of potential drugs, then plucking out the most promising candidates for further study.
Miller's system shifts the burden of the most painstaking drug-development work off the shoulders of technicians and onto tiny molecules, which assemble themselves into countless combinations and then go through a Darwinian process that closely mirrors how nature finds the best compound for a job. If the technology can be expanded for industrial use, it would offer a faster way for chemists to create and screen potential new drugs.
"The approach shows great promise because it's fundamentally more efficient," says Paul Wender, professor of chemistry at Stanford University and an expert in the synthesis of biochemical and medicinal compounds. "The Miller group has clearly shown that this approach makes sense and that it can work. Nature is a huge biodiversity generator, and they've found a way to mimic this process in the laboratory."
Miller's technique relies on atoms of transition metals, such as zinc or cadmium, to build vast libraries of thousands of potential drugs. Just as a skilled host can facilitate socializing between strangers at a cocktail party, these atoms of zinc and cadmium pair up small molecules known as monomers, searching for a fruitful combination. Everyday chemistry then goes to work to "decide" which of the resulting compounds best matches the prospective drug's DNA, RNA, or protein targets, which cause disease. The very best match elbows out all the others to latch onto the target molecule.
"With our technique, we try to find molecules to bind
receptors in much the same way nature has for millions of years,"
says Miller, an assistant professor of chemistry. "We take a
receptor we want to target, add many little molecules to it, and
see which ones are best at binding the recept
Contact: Steve Bradt
University of Rochester