Engineering of SH2 Domains for the Recognition of Protein Tyrosine O-Sulfation Sites

Protein engineering has brought advances to industrial processes, biomaterials, nanotechnology, biosensors, and biomedical applications. This chapter will focus on the engineering of Src Homology 2 domains (SH2) to act as an antibody mimetic for the recognition of sulfotyrosine-containing peptides or proteins. In comparison to anti-sulfotyrosine antibodies, SH2 mutants have much smaller size and can be heterologously expressed and purified in large quantity at low cost. This chapter will describe the use of phage display to identify a sulfotyrosine-binding SH2 mutant and the subsequent enrichment of sulfotyrosine-containing peptides in complex biological samples.