CHAPTER 7: Molecular Glues for Protein Assembly

Precision, bottom–up fabrication of protein-based materials provides a basis for new types of devices that can serve societal needs. However, the incorporation of proteins (e.g. enzymes) into materials is challenged by the intricacy of protein surfaces and their interactions. Consequently, controlled protein assembly (e.g. crystallization) is an enabling technology that will spur future biotech developments. Numerous methods of controlled assembly are available. This chapter presents examples of small molecule building blocks that direct protein assembly. We focus on the features of molecular recognition and assembly as evidenced by X-ray crystallography. The building blocks are in many cases typical supramolecular ligands and include: five types of macrocycle, five types of extended aromatics comprising naphthalene or larger groups and other structures with varying degrees of water-solubility. There is a particular focus on the contribution of anionic calixarenes. Considering their special roles in protein crystallization and structure determination, we have included also two types of metal-containing building block. Overall, the examples include about fifty different proteins. In this way, we illustrate the great diversity of molecular glues for protein assembly and the fabrication of crystalline frameworks. In parallel, we highlight the ongoing opportunities at the interface of protein science and supramolecular chemistry.