illustration by Leif Parsons

Lego for the Lab

Synthesizing a molecule is a lot like doing a jigsaw puzzle. You start with many pieces, figure out how they fit together, and eventually, after a lot of trial and error, you’re done. HHMI Early Career Scientist Martin Burke has come up with a way to simplify the process using Lego-like building blocks that take the puzzling out of synthesis.

Burke and his team at the University of Illinois at Urbana-Champaign analyzed almost 3,000 polyenes found in nature. These molecules—commonly used as drugs, pigments, and fluorescent probes—contain chains of carbon atoms connected by alternating single and double bonds. The scientists realized that more than three-quarters of the natural products could be created with only 12 different chemical building blocks joined by a single type of coupling reaction. Like 12 pieces of Lego that can be combined to make just about anything, from a house to a dinosaur, the researchers mixed and matched the basic polyene building blocks to produce several different molecules.

Martin Burke explains how his research group breaks down complex chemicals into simple “building blocks.”

The discovery, reported in the June 2014 issue of Nature Chemistry, provides chemists with a simple way to build polyenes that are challenging or too expensive to extract from their natural sources. Burke eventually hopes to expand his chemical Lego set to include more than just polyenes. “This paper covers about 1 percent of all natural products isolated to date,” he says. “We want to determine how many building blocks it takes to reach most of the remaining 99 percent, and to create a highly optimized machine that can automatically stitch those building blocks together.”