A Hyperstable Minimalist Protein for Molecular Recognition
Antibodies represent the most rapidly growing class of therapeutic proteins. In recent years, various studies have demonstrated that multispecific antibodies often show enhanced therapeutic potency compared to normal IgG. Multispecific antibodies can be constructed by fusing small binding proteins to IgG. Desired properties of those small binding scaffolds include high stability, high expression yield, small size, high solubility, low aggregation and negligible stickiness. Although various binding scaffolds have been introduced recently, none of these can as yet be considered an optimal solution to the problem.
Therefore, in the present study we aim to develop a novel binder scaffold based on a highly stable protein from a hyperthermophilic organism. First, we will further improve the biophysical properties of this protein by computational design. Based on the optimized scaffold, a library containing mutated surface residues will be displayed on yeast and subsequently used for the selection of binders against a variety of model antigens. We expect that this library based on the optimized scaffold will enable the rapid development of highly stable binders. Those will in turn facilitate efficient construction of multispecific antibodies.