Selenocysteine Chemistry and Total Chemical Synthesis Applied for Accessing Human Selenoproteins

Once considered a toxic element, selenium is now known as an essential element for life. For example, in humans it is incorporated in proteins known as selenoproteins containing the 21^st encoded amino acid selenocysteine (Sec). The differences between selenium and sulfur in their redox potentials, pK_as, and nucleophilicities and electrophilicities give selenium interesting chemistry. For example, Sec can be used as a tool for chemical protein synthesis, and allowing for site selective modifications. It can be also incorporated into protein sequences to enhance oxidative protein folding. This lecture will discuss our recent studies on chemical protein synthesis using Sec and selective deselenization reactions, which convert Sec into Ala or Ser.

These advances in chemical protein synthesis bring us closer to accessing naturally occurring selenoproteins, especially human selenoproteins that still await functional characterization.