An Unexpected Example of Protein‐Templated Click Chemistry

Abstract

It all happened with a click: In a search for histone deacetylase (HDAC) inhibitors using in situ click chemistry, the first example of protein–Cu acceleration of the azide–alkyne cycloaddition reaction was uncovered. The copper center in the protein target HDAC8 catalyzed triazole formation between one azide–alkyne pair among 30 possibilities. These results provide a new route to HDAC inhibitors and a precedent for new types of protein-based catalysts for click chemistry. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.