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Atomic-Level Insights into How Polymers Improve Protein Therapeutics

Published December 12, 2022

The colored regions of the protein in the above schematic were revealed to be interacting with the polymer
The colored regions of the protein in the above schematic were revealed to be interacting with the polymer

Using NMR, researchers determined a molecular model of a protein-polymer conjugate, providing new insights into how polymers can be used to make protein drugs more robust.

What did the scientists discover?

A collaborative team of chemists, biochemists, and structural biologists were able to attach a polymer to a protein and determine how the polymer can improve the potential to develop the protein into a therapeutic drug. Polyethylene glycol (PEG), a commonly used polymer was found to improve the stability of a protein to make it more useful as a potential therapeutic for treating cancers and inflammatory diseases.


Why is this important?

Proteins are promising therapeutics, but are typically unstable in the human body. Also biologics, including PEGylated proteins, are increasingly used as therapeutics, but there is little experimental data on how polymers impact the properties of biologics. Using NMR, the Eddy lab provided mechanistic insight into how polymers increase the thermal stability of proteins in conjugates. This data will be expanded in studies that provide a rational for designing protein-polymer conjugates with predictable chemical properties.


Who did the research?

A Pritzlaff, G Ferré, E Mulry, L Lin, N Gopal Pour, DA Savin, ME Harris, MT Eddy

University of Florida, Department of Chemistry


Why did they need the MagLab?

To observe the protein-polymer conjugates, the research team needed the high magnetic fields and sensitive NMR instrumentation provided by the instruments at the MagLab’s AMRIS Facility.


Details for scientists


Funding

This research was funded by the following grants: G.S. Boebinger (NSF DMR-1644779); M.T. Eddy (NIH R35GM138291); E. Mulry (NIH T32 GM136583); M. Harris (NIH R35GM127100)


For more information, contact Joanna Long.

Tools They Used

This research was conducted in the 800 MHz NMR instrument with a cryogenic probe at the MagLab's AMRIS Facility located at the University of Florida.

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Last modified on 28 December 2022