Since the invention of hybridoma technology, methods for generating affinity reagents that bind specific target molecules have revolutionized biology and medicine. In the postgenomic era, there is a pressing need to accelerate the pace of ligand discovery to elucidate the functions of a rapidly growing number of newly characterized molecules and their modified states. Nonimmunoglobulin-based proteins such as DARPins, affibodies, and monobodies represent attractive alternatives to traditional antibodies as these are small, soluble, disulfide-free, single-domain scaffolds that can be selected from combinatorial libraries and expressed in bacteria. For example, monobodies—highly stable scaffolds based on the immunoglobulin VH-like 10th fibronectin type III (10Fn3) domain of human fibronectin—have yielded antibody mimetics that bind to numerous targets for applications including intracellular inhibition, therapeutics, and biosensors. These 10Fn3-based ligands can be derived from highly diverse libraries using techniques such as phage, ribosome, mRNA, bacterial, and yeast displays.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747967PMC
http://dx.doi.org/10.1002/anie.201101149DOI Listing

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