New cages to trap molecules push boundaries of protein design | 6/18/2019 | Staff
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Protein design is a popular and rapidly growing field, with scientists engineering novel protein cages—capsule-like nanostructures for purposes such as gene therapy and targeted drug delivery. Many of these structures fashioned in the lab, while perhaps aesthetically pleasing to chemists, have holes too big to trap a target molecule or don't open on command, limiting their functional scope.

But new research findings, by UC San Diego Professor of Chemistry and Biochemistry Akif Tezcan, offer a protein architecture with small holes—"pores" in chemistry jargon. The findings, published in Nature, push the boundaries of synthetic protein design past what is considered state-of-the-art.

Molecules - Forth - Holes - Things - Inside

"If molecules can freely go back and forth through these holes, you're not going to be able to store little things on the inside," explained Tezcan. "Protein cages that people have designed before have the right shape and symmetry, but they're mostly like Wiffle balls—they don't necessarily isolate the interior from the exterior."

By tailoring the surface of small protein building blocks with multiple metal-binding sites, Tezcan's team developed a new protein cage with small pores that trap molecules securely inside.

Project - Addition - Field - Design - Protein

"This project is a significant addition to the field because it demonstrates that minimal design can be used to generate modular, stimuli-responsible protein cages that approach the complexity of naturally evolved systems," said co-author Rohit Subramanian, a graduate student in the Tezcan Lab.

Additionally, the new structure can be opened via chemical, thermal or redox (transfer of electrons between a set of atoms, molecules or ions with the same chemical formula) reactions. According to Tezcan, the UC San Diego research team was ideally situated to create the new protein cage design with its inorganic chemistry insights—specifically metal coordination chemistry, which made the difference.

Author - Paper - Constructing - Protein - Polyhedra

The first author of the paper, titled "Constructing Protein Polyhedra via Orthogonal Chemical Interactions," is Eyal Golub, a former postdoctoral scholar in...
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