Proteins have wide applications in research and industry due to their substrate specificity and biological function. However, protein instability during transport, storage, and delivery increases costs for both patients and researchers. As a result, excipients such as small molecules, salts, or amino acids are often added as stabilizers. Herein we report a library of well-defined polyesters with bioinspired saccharide substituents that can be used to stabilize proteins. A common alkene-containing degradable backbone was synthesized using ring-opening polymerization (ROP) and multiple potential stabilizers were installed using highly efficient thiol-ene chemistry. This approach enabled the direct comparison of side chains without differences in degree of polymerization. The polymers were used to stabilize the therapeutic protein granulocyte-colony stimulating factor against activity loss from storage and thermal stress. Additionally, the molecular weight of the polyesters was varied and larger polymers demonstrated improved protein stabilization. This synthetic approach offers a new platform for biocompatible and degradable protein stabilizers that enables the rapid screening of novel excipients.

Synthesis of a library of degradable and protein-stabilizing polyesters using thiol-ene post-polymerization modification

253rd National Meeting (2017)

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