Abstract

Synthetic Antigen Binders (sABs) are a new class of antibody-based reagents engineered using novel phage display libraries. Using the power of phage display selection, it is possible generate sABs that: 1) target specific regions on the surface of a protein, 2) recognize specific conformational or oligomeric states, 3) induce conformational changes, and 4) capture and stabilize multi-protein complexes. Using these attributes, we can generate sABs that have their own functional properties and when introduced into cells can alter biological processes in defined ways. We have also employed them as crystallization chaperones to capture proteins in their most relevant states. As an example, the structure of the full-length KcsA potassium channel in both its closed and open states will be discussed. Further, we have also developed a cell delivery system that provides for introducing fully functional sABs into the cytoplasm for live cell imaging applications and to selectively alter cellular function.