Scientists dream of the day when they can create designer proteins capable of inhibiting harmful interactions, modifying substrates or guiding cellular machines to where they are needed within the body. Though that dream may be far down the road, Yale chemist Alanna Schepartz took an important first step forward two years ago, when she and her team created the first synthetic protein in the lab.
Now the National Science Foundation has awarded Schepartz a grant, worth more than $500,000 over the next three years, to continue the work that led to that breakthrough — one which Chemical & Engineering News called one of the year’s “most important research advances” in the field of chemistry.
“Creating artificial proteins is somewhat of a holy grail,” says Schepartz, the Milton Harris ‘29 Ph.D. Professor of Chemistry and professor of molecular, cellular and developmental biology. “A fair number of people thought it would be impossible to synthesize a molecule that could come close to behaving like a natural protein that has benefited from billions of years of evolution.”
Working with former graduate students and postdocs Jade Qiu and James Petersson, both now at the University of Pennsylvania, and Douglas Daniels, now at Novartis, Schepartz created a short ß-peptide that assembles into an “octameric bundle” shape that exhibits all the traits of natural bundle proteins, but with some additional potential benefits.
“Unlike natural peptides and proteins, ß-peptides are not broken down by enzymes, not altered significantly by metabolism and seem not to jump-start the immune system the way a foreign natural protein can,” Schepartz says. That means scientists may one day be able to design drugs with all the functions of natural proteins, but which won’t be broken down by the body.
The new funding will allow Schepartz and members of the bundle team — Cody Craig, Jessica Goodman, Matthew Molski and Jonathan Miller — to take several important steps forward, by defining the rules of sequence and structure that control whether a ß-peptide assembles into a bundle and what shape it assumes when it does. It will also allow them to develop high-throughput fluorescence screens to identify stable bundles from mixtures of hundreds of ß-peptides, as well as explore ß-peptide bundles as potential catalysts for synthetic transformations.
— By Suzanne Taylor Muzzin
