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Protein Sci. 2017 May;26(5):910-924. doi: 10.1002/pro.3148. Epub 2017 Mar 24.

Monobodies and other synthetic binding proteins for expanding protein science.

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Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, 60637.
Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, 10016.
Department of Biochemistry and Molecular Pharmacology New York University School of Medicine, New York, NY, 10016.


Synthetic binding proteins are constructed using nonantibody molecular scaffolds. Over the last two decades, in-depth structural and functional analyses of synthetic binding proteins have improved combinatorial library designs and selection strategies, which have resulted in potent platforms that consistently generate binding proteins to diverse targets with affinity and specificity that rival those of antibodies. Favorable attributes of synthetic binding proteins, such as small size, freedom from disulfide bond formation and ease of making fusion proteins, have enabled their unique applications in protein science, cell biology and beyond. Here, we review recent studies that illustrate how synthetic binding proteins are powerful probes that can directly link structure and function, often leading to new mechanistic insights. We propose that synthetic proteins will become powerful standard tools in diverse areas of protein science, biotechnology and medicine.


biologic therapeutics; directed evolution; protein engineering; protein-protein interaction; structure-function relationship

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