Stephen B. H. Kent

Professor Stephen B. H. Kent invented native chemical ligation, the reaction that enabled practical total chemical synthesis of proteins. This technology transformed peptide chemistry into a tool for creating novel protein molecules with atomic precision, opening new dimensions in protein science.

Kent served on the faculty at Scripps Research before joining the University of Chicago, where he is Professor of Chemistry and of Biochemistry and Molecular Biology. He directed the Institute for Biophysical Dynamics from 2003 to 2009 and founded two biotechnology companies, Ciphergen Biosystems and Gryphon Sciences.

In 1994, Kent and his student Philip Dawson reported native chemical ligation in Science. The reaction exploits the chemoselective condensation of an unprotected peptide bearing a C-terminal thioester with another unprotected peptide containing an N-terminal cysteine. An initial thioester-linked intermediate undergoes spontaneous rearrangement to form a native peptide bond. The method works in aqueous solution at neutral pH and is applicable to peptide segments regardless of size.

Native chemical ligation enabled the synthesis of proteins exceeding 200 amino acids, including HIV-1 protease, human lysozyme and erythropoietin. Kent exploited the power of synthesis to create mirror-image proteins, revealing that racemic protein crystallization facilitates structure determination by X-ray diffraction. His laboratory also prepared covalently linked protein heterodimers and backbone-engineered enzymes inaccessible through biosynthesis.

Kent's honors include the Ralph F. Hirschmann Award, the inaugural Kaiser Award from the Protein Society, the Merrifield Award, the Rudinger Medal, the Akabori Medal and the Alfred Bader Award in Bioorganic Chemistry.