Good chemistry between proteins and materials

Reversibly modifying 3D biomaterials with active proteins would greatly improve the control of cell function in vitro. Attaching full-length proteins to materials, such as hydrogels, requires the introduction of chemical groups in the protein structure that react with the material without compromising protein activity. Now, writing in Nature Materials, Cole DeForest and colleagues report a site-specific chemoenzymatic protein modification strategy that maintains protein activity and, in combination with photochemistry, allows the spatially and temporally controlled photopatterning of hydrogels in 3D.

DeForest and colleagues use a chemoenzymatic strategy to site-specifically functionalize proteins with bioorthogonal reactive groups. By fusing proteins to the bacterial transpeptidase sortase, which recognizes a specific sorting signal appended to the protein, a tag can be conjugated to the protein through subsequent nucleophilic displacement of the enzyme with a polyglycine peptide. “This strategy enables virtually any polyglycine-containing peptide to be appended quantitatively onto the C-terminus of recombinant proteins — a feature that we have exploited to install several different bioorthogonal reactive groups site-specifically onto many proteins of interest,” explains DeForest.