Pegylation of the Galectin-3 carbohydrate recognition domain creates a kinetic trap protecting the protein from thermal unfolding

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Proteins are widely used as therapeutics but often can be unstable, limiting their applications in the clinic. To improve the stability of protein drugs, synthetic polymers such as polyethylene glycol (PEG) can be covalently attached to specific protein side chains, creating protein-polymer conjugates. Though nearly thirty PEGylated proteins have been FDA-approved, our understanding is very limited of how PEG-protein interactions alter the fundamental chemical and physical properties of the conjugate.