Protein stapling via azide–alkyne ligation

Here we demonstrate a methodology, termed protein stapling, for the introduction of covalent constraints into recombinant proteins. Using the azide–alkyne click reaction as the stapling chemistry, we have improved the thermostability of a model leucine zipper protein. Additionally, stapling the core of the small, globular protein G resulted in improved binding to its target, immunoglobulin G.