Synthetic antibodies evolved from a minimal genetic code and their applications to structural and cell biology.
April 7, Tue 2009
1:00 pm, MRB 100 Conference Room
Dr. Anthony Kossiakoff
Department of Biochemistry & Molecular Biology, University of Chicago
A powerful bipartite technology platform has been developed to produce a novel class of synthetic antigen binders (sABs). sABs are antibody-like molecules engineered by phage display mutagenesis to bind with high affinity and specificity to a broad range ofbiomolecules including protein complexes, membrane proteins and even functional RNAs. A key component of the approach is the development of phage display libraries that utilize only a fraction of the available genetic code. We use these sABs as crystallization chaperones to help induce crystallization of recalcitrant high impact structural biology targets. We couple the potential of the sAB technology with a novel cellular delivery system that permits us to introduce sABs (and other entities, even quantum dots or entire phage capsids) into live cells without perturbing the cell membrane. We call this process “Receptor-Mediated Delivery” (RMD), and it has allowed us to deliver fluorescently labeled sABs and motor proteins into the cytoplasm of live cells in their fully function form for imaging dynamic cytoskeletal remodeling events.