SAN DIEGO Duke University chemists have used "combinatorial chemistry" techniques to synthesize a compound originally extracted from an African fungus that could lead to oral drugs that control diabetes.
The compound, called demethylasterriquinone B1 or "DAQ" for short, "has this fascinating property of being able to activate insulin receptors in cells in basically the same way as insulin, and yet it's not a protein," said Michael Pirrung, a Duke chemistry professor who prepared his team's work for presentation Wednesday at the American Chemical Society's national meeting in San Diego.
"Instead, it's just a regular organic molecule like you take for your allergies. And because it's a regular organic molecule you can take it orally, which is such a big deal," Pirrung added in an interview at Duke. Insulin to treat diabetes requires injections. "The other big thing is that it's a naturally occurring molecule," he noted. "And one area that combinatorial chemistry has previously not really made any inroads into is naturally occurring compounds."
Combinatorial chemistry seeks to efficiently synthesize and identify chemicals with desired traits by mixing and matching large "libraries" of different molecular building blocks to eventually create the desired structure. Pirrung helped pioneer "solid phase synthesis" techniques for performing combinatorial chemistry reactions on the surfaces of small glass chips.
However, "the DAQ molecule is not particularly amenable to synthesis while its pieces are attached to a solid," he said. Fortunately, Pirrung noted, "the principles of combinatorial chemistry have now been expanded to molecules that are made in solution."
Instead of fixing molecular libraries to a surface, tiny samples of each library entry can be placed in a different small well, with different reagents then pipetted in to interact there, he said.