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Web Date: April 30, 2012

Polymer Protects Proteins

Biochemistry: Glycopolymer guards proteins against heat and freeze-drying better than current stabilizers
Department: Science & Technology | Collection: Life Sciences
News Channels: Biological SCENE, JACS In C&EN
Keywords: trehalose, glycopolymers, protein stability, polyethylene glycol, PEG, protein drugs
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Double Duty
A trehalose-based polymer (chemical structure, right) can protect an attached protein (ribbon structure, left) from heat or freeze-drying.
Credit: J. Am. Chem. Soc.
chemical structure linked to ribbon structure
 
Double Duty
A trehalose-based polymer (chemical structure, right) can protect an attached protein (ribbon structure, left) from heat or freeze-drying.
Credit: J. Am. Chem. Soc.

Protein-based drugs can quickly lose activity during transport and storage. To prolong the proteins’ activity, drug firms add stabilizers, including polyethylene glycol and trehalose, a disaccharide that some organisms use to protect themselves from dehydration.

Now Heather D. Maynard and her research team at the University of California, Los Angeles, have combined the two molecules to create trehalose glycopolymers that protect proteins from heat and freeze-drying better than trehalose or PEG (J. Am. Chem. Soc., DOI: 10.1021/ja2120234).

The material’s monomers consisted of trehalose connected through a short linker to a molecule based on triethylene glycol. After polymerization, the researchers attached the polymer to lysozyme, an enzyme that they knew is sensitive to heat and freeze-drying.

The researchers then heated the glycopolymer-protected protein samples, simulating temperature changes during shipping, and freeze-dried other samples, a common protein storage-preparation method. They compared those samples to similarly treated samples of protein that they had mixed, but not chemically linked, with glycopolymer, trehalose, or PEG. Using a fluorescent assay for lysozyme activity, they found that the activity of the glycopolymer-attached protein was as much as five times as high as that of the protein mixed with PEG or trehalose. It was similar or higher, depending on conditions, to that of the protein mixed with the glycopolymer.

Maynard is now testing the glycopolymer with protein drugs and evaluating how it stabilizes proteins. She thinks that by attaching it to proteins, the researchers ensure high concentrations of it near the protein to shield against environmental stresses.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

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