Engineering of binding functions into proteins.

Initially emerging as a highly innovative concept in the late 1990s, the concept of creating novel binding reagents based on stable protein scaffolds from outside the immunoglobulin (Ig) superfamily has become a well-developed area of research and discovery today. Numerous scaffolds based on extracellular, membrane-bound or intracellular proteins (or their domains) have been recruited, yielding versatile research reagents and even biological drug candidates to serve as a viable alternative to antibodies. This minireview discusses both established and novel concepts in this field and summarizes the current state of clinical development of the more advanced protein scaffolds, in particular Affibody, Adnectin, Anticalin and DARPin drug candidates.