Adding Function to Protein Scaffolds.

Biological systems often outperform artificial ones in ordering, assembly, and diversity of structure at the nanoscale. Proteins are particularly remarkable in this context. Through oligomerization, protein monomers assemble on multiple length scales, into larger and more complex structures such as viral capsids, filaments, and regulatory complexes. It is this structural diversity that makes proteins attractive candidates for use as functionalizable scaffolds. Well-established protein structure databases such as the protein data bank (PDB) allow researchers to search for a structure that fits their requirements, allowing them access to shapes and assembly mechanisms that would otherwise be difficult to achieve. Then, by employing functionalization techniques to conjugate artificial or biological molecules to their protein scaffold of choice, researchers can access chemistries beyond the limits of the 20 commonly occurring natural amino acids. Additionally, proteins, with a few exceptions, operate at physiological pH and temperature, making them ideal for medical applications and/or low-cost manufacture. Additionally, proteins sourced from extremophiles such as Thermus aquaticus (a bacterial species sourced from hot springs) display stability across a wide range of temperatures, expanding the scope for scaffold selection. This chapter will cover some of the common methods of protein functionalization as well as some specific examples of popular functionalization methods reported in the literature. It will then present three case studies showing examples of how functionalization and imaging of proteins and protein-based structures can be achieved.