Site-Selective Protein Modification: From Functionalized Proteins to Functional Biomaterials

Abstract

Chemists, biologists, and material scientists alike have long sought to control protein presentation, orientation, and activity within biomaterials to dictate reaction catalysis, biological signaling, and cell-fate specification. Such control is most typically achieved through the installation of reactive chemical handles onto proteins that govern static or dynamic biomacromolecule-material associations. Though convenient, stochastic functionalization strategies often yield illdefined protein samples with severely diminished activity. In contrast, site-selective methodologies permit the controlled installation of material-interacting handles onto fragile proteins while preserving native structure and function.Here, we review methods that afford chemical, regioselective, and site-specific modification of proteins, emphasizing those that have found utility in the creation of functional biomaterials. We discuss cutting-edge strategies involving small-molecule-based labeling, genetic engineering, and chemoenzymatic reactions that provide precise control over the extent and location of protein modification. We assess the progress and look to the future in exploiting these functional proteins to create next-generational biomaterials for tissue engineering, therapeutic, and fundamental biological applications.

Intracellular Antibody Delivery Mediated by Lipids, Polymers, and Inorganic Nanomaterials for Therapeutic Applications

“…However, if the system is designed carefully as to not impair the function, opportunities exist to develop new and improved antibody loading strategies by modifying the cargo to include chemical properties not found in natively expressed antibodies. Previously reported techniques applied in protein modification [ 21,230–232 ] and antibody‐drug conjugation [ 233,234 ] systems can be useful. For example, the antibody cargo itself may be imparted with some improved organ‐ or cell‐specific targeting, or may be modified to more easily complex with another noncovalent delivery system.…”

A single amino acid Gly-tag enables metal-free protein purification

“…The robust immobilization through C-C bond formation facilitates ordered single-site immobilization and opens a gateway for developing other biochemical tools and biomaterials. [23][24][25][26] Alongside, we selected myoglobin (1b, N-Gly) and SUMO1 (1d, N-Gly) to re-validate the efficiency of the Gly-tag purication resin ( Fig. S5 and S8 †).…”

Surface Immobilization Chemistry of a Laminin-Derived Peptide Affects Keratinocyte Activity

“…These factors affect surface density, orientation/domain exposure, peptide intra- and intermolecular structure, and overall biological activity. One easily controllable factor in these systems is the immobilization chemistry [ 23 ]. In general, immobilization chemistries are divided into two classes based on whether they are chemoselective or not.…”