Ronald Breslow Award for Achievement in Biomimetic Chemistry | Chemical & Engineering News
Volume 84 Issue 1 | p. 29 | Awards
Issue Date: January 2, 2006

Ronald Breslow Award for Achievement in Biomimetic Chemistry

Department: ACS News

Sponsored by the Breslow Endowment

Barbara Imperiali isn't scared to try new things. A professor of chemistry and biology at Massachusetts Institute of Technology, she is one of the most fearless and creative scientists working at the interface of chemistry and biology, her colleagues say.

Undaunted by the complexity of biological systems, Imperiali, 49, has used her synthetic know-how to probe how and why proteins are glycosylated in vivo, to investigate complex signal transduction pathways, and to make sensors of metal ions such as zinc. Underpinning all of her work is her ability to devise "chemical tools that will allow biologists to answer questions in vivo that are presently inaccessible," says her MIT colleague JoAnne Stubbe.

"My early training in chemical synthesis has colored my entire career," Imperiali admits. Born in England, she received an undergraduate degree in medicinal chemistry from University College London in 1979. She then left England for MIT, where she earned a Ph.D. in synthetic organic chemistry under the guidance of Satoru Masamune.

Having always known she wanted to keep one foot in chemistry and the other in biology, Imperiali then turned her synthetic skills to biological questions during postdoctoral stints at MIT and Brandeis University.

Glycosylation was one of the first biological problems that Imperiali tackled when she started her academic career at Carnegie Mellon University. Even though the problem at times seemed intractable, she pressed on when she moved to California Institute of Technology a few years later. Today, having risen through the ranks to full professor at Caltech before moving to MIT in 1999, "I'm proud that we stuck with this fascinating system," she says. "It continues to yield surprises."

Imperiali has taken a multidisciplinary approach to studying glycosylation. "There is no technique that we're afraid to try if it will shed light on a problem," she says. She has designed and synthesized small peptides and has used them to probe the mechanism of a key glycosylation enzyme known as oligosaccharyl transferase. This multimeric, membrane-bound enzyme attaches sugar residues to asparagine residues in proteins.

Using chemical synthesis, multidimensional nuclear magnetic resonance spectroscopy, and molecular modeling, Imperiali also has examined how asparagine-linked glycosylation modulates protein folding. She has extended these studies to probe how proper glycosylation inhibits the formation of insoluble protein fibrils like those associated with neurodegenerative diseases such as Alzheimer's.

Recently, Imperiali has turned her synthetic skills to probing signal transduction, particularly the role played by ubiquitous signaling enzymes known as kinases. Her peptide-based fluorescence chemosensors for monitoring kinase activity are "precisely the kind of technology needed for quantitative, dynamic studies of cell-signalling networks," notes MIT biological engineer Douglas Lauffenburger.

The technology works for many kinases and is now being commercialized, Imperiali notes. In addition, her team has made caged phosphopeptides that can be "unmasked" by light, "offering a wonderfully clever way to probe the effects of a kinase-mediated substrate phosphorylation in a controlled fashion," Lauffenburger says.

In an extension of this approach, Imperiali's lab has also designed peptide-based fluorescent chemosensors of metals such as zinc. She's also showed that short terbium-binding peptides can be used as luminescent "tags" for labeling and tracking proteins.

Imperiali is a member of the American Academy of Arts & Sciences and a fellow of the Royal Society of Chemistry and has garnered several awards including the Arthur C. Cope Scholar Award.

The award address will be presented before the Division of Organic Chemistry.—Amanda Yarnell

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