Marker Seminar: Applications of SuFEx Click Chemistry for Drug Discovery and Chemical Biology

Prof. Barry Sharpless (2001 and 2022 Nobel Laureate in Chemistry), Scripps Research Institute

My work has been guided by the modular simplicity of nature -- the fact that all molecules of life are made from several dozen building blocks. Here I will discuss the Sulfur(VI) Fluoride Exchange (SuFEx), a second near-perfect click chemistry reaction pioneered here at Scripps. SuFEx allows reliable molecular connections to be made under metal-free conditions. I will include applications in drug discovery, chemical biology, and polymer chemistry.

Dr. Sharpless' >50-year research career has been devoted to finding new tools and better general methods for exploring the chemical universe. He shared the 2001 Nobel Prize in Chemistry for his work on chirally catalyzed oxidation reactions. In 2022, Barry was awarded the Nobel Prize in Chemistry for developing “click chemistry”, making him only the second scientist to win two Nobels in Chemistry. Click chemistry, a discovery methodology based on the insight that the molecules of life are made from less than several dozen small building blocks, provides a reliable way to uncover useful chemical function and spring-loaded ‘perfect’ reactions.

Today the focus of the Sharpless lab is Sulfur(VI) fluoride exchange (SuFEx) click chemistry, which allows reliable molecular connections under metal-free conditions. SuFEx has applications in synthetic methodology; chemical biology and drug discovery; and polymers and material science. Barry received his BA from Dartmouth College in 1963 and his PhD in Chemistry from Stanford University in 1968. Before joining Scripps Research in 1990, he was chemistry faculty at MIT and Stanford.