Chemical protein synthesis has been established as a powerful methodology for the preparation of peptides and proteins enabling rapid interrogation of structure activity relationships and assessment of the importance of post translation modifications. Access to larger targets of interest has been facilitated by a large effort towards the development of  technologies which facilitate the production of native protein structures through multi-segment ligation strategies.  

We have investigated the chemical synthesis of Insulin-like growth factor binding protein 2 (IGFBP-2), a cysteine rich protein which has attracted attention for its ability to regulate glucose metabolism with antidiabetic effects in mice. Previous studies have reported that Serine 106 is phosphorylated in vivo raising questions towards the importance of this post translational modification. This work highlights the potential of diselenide-selenoester ligation and native chemical ligation towards accessing complex protein targets.