ICOS-20, 20th International Conference on Organic Synthesis
Friday, 20 October 2017
Stephen Kent


KentStephen Kent

Current Appointments
Professor of Chemistry
Professor of Biochemistry & Molecular Biology
Institute for Biophysical Dynamics
The University of Chicago


B.Sc., Victoria University of Wellington, New Zealand
M.Sc., Massey University, New Zealand
Ph.D., University of California, Berkeley

Leach Medal, Lorne Conference on Protein Structure and Function
Bader Award in Bioorganic Chemistry, American Chemical Society
Akabori Award, Japanese Peptide Society
Rudinger Award, European Peptide Society
Merrifield Award, American Peptide Society
du Vigneaud Award, American Peptide Society
Kaiser Award, The Protein Society
Hirschmann Award, American Chemical Society
Honorary Fellow, Royal Society of New Zealand
Fellow, Royal Society of Chemistry
Honorary Life Member, Israel Chemical Society
Fellow, American Association for the Advancement of Science


Stephen Kent invents new synthetic chemistries and uses them to elucidate the molecular basis of protein function. His early work focused on understanding the underlying physical chemical principles of polymer-supported peptide synthesis ('solid phase peptide synthesis' (SPPS)), and on identifying and eliminating the chemical side reactions affecting SPPS. The resulting highly optimized methods for the chemical synthesis of peptides were applied to studies of the hepatitis B virus and HIV. This work culminated in elucidation of information critical for the development of effective hepatitis B vaccines, and in the use of total chemical synthesis to prepare protein for the determination (with collaborators) of the original crystal structures of the HIV-1 protease molecule complexed with canonical inhibitors. These HIV-1 protease structural data formed the basis of the highly successful, worldwide programs in structure based drug design that led to the development of the ‘protease inhibitor’ class of AIDS therapeutics.

In the 1990s, Stephen Kent pioneered a radically new approach to the total synthesis of proteins based on ‘chemical ligation’: chemoselective reaction of unprotected peptide segments in aqueous solution. The chemical ligation principle, embodied in native chemical ligation and kinetically controlled ligation, has enabled the fully convergent total synthesis of large protein molecules and the consequent general application of physical and organic chemistry to the world of proteins.

The focus of the Kent laboratory at The University of Chicago is to understand the chemical basis of protein function, and to demonstrate that knowledge by the design and construction of protein molecules with novel structures and properties. In the past few years, the Kent lab has pioneered the use of mirror image D-protein molecules to enable the determination of the X-ray structures of recalcitrant proteins by racemic and quasi-racemate crystallography. Even more recently, the Kent lab has reported the first efficient route to a total chemical synthesis of human insulin, making use of a unique ester-linked surrogate proinsulin. Currently, we are employing a systematic chemical protein synthesis plus protein phage display approach to the development of mirror image D-proteins as a novel class of molecules for antagonizing the action of natural protein molecules. Such D-protein antagonists may have significant advantages as human therapeutics