Jeremy R. Knowles

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Jeremy R. Knowles
Born(1935-04-28)28 April 1935
Died3 April 2008(2008-04-03) (aged 72)
Alma materOxford University
Known forEnzyme catalysis
AwardsWelch Award in Chemistry (1995)
Scientific career
FieldsBiochemistry
InstitutionsHarvard University
Doctoral studentsHagan Bayley[1]

Stephen L. Buchwald

Ronald T. Raines

Jeremy Randall Knowles, CBE, FRS (28 April 1935 – 3 April 2008) was a professor of chemistry at Harvard University, was Dean of the Harvard University Faculty of Arts and Sciences from 1991 to 2002. He joined Harvard in 1974, received many awards for his research, and remained at Harvard until his death, leaving the faculty for a decade to serve as Dean. Knowles died on 3 April 2008 at his home.[2]

In 2006, he was selected by incoming interim president Derek Bok to return to his position as Dean of the Faculty of Arts and Sciences on an interim basis, replacing William C. Kirby, who was ousted by now former president Lawrence Summers.[3]

Biography[edit]

Knowles was born in England in 1935, educated at Magdalen College School, Oxford and Balliol College, Oxford (BA 1959, DPhil 1961). He was a Pilot Officer in the Royal Air Force. During his undergraduate he did research in Richard Norman's physical organic chemistry laboratory. There, he studied electronic effects on the rates of aromatic substitution reactions. In 1960, he became a research lecturer at Oxford. He later became Fellow and Tutor at Wadham College, Oxford. In 1961, he took a post-doctoral fellowship at the California Institute of Technology, working with George S. Hammond, who was an organic photo-chemist. Together, they found that some catalyzed reactions can occur up to one-million times faster than non-catalyzed reactions. Intrigued by this discovery, Knowles became an enzymologist. For a brief time, Knowles was a visiting professor at Yale University. in 1974, Knowles moved his research group to Harvard and became a professor there.

Knowles married Jane Sheldon Davis in 1960, and together they had three sons.

Work[edit]

Knowles's research was on the boundary of chemistry and biochemistry, and concerned the rate and specificity of enzyme catalysis and the evolution of enzyme function. Early in his career, Knowles studied α-chymotrypsin and pepsin, which are nonspecific proteases, meaning they accept a broad range of substrates. He researched what made these enzymes nonspecific and how they increased the rate of peptide-bond hydrolysis. In 1972, Knowles developed a method for photo-affinity labelling, enabling the formation of a covalent bond between a protein and a ligand under the control of light.

Knowles then began seminal studies on the glycolytic enzyme triosephosphate isomerase (TIM). He took advantage of its simplicity—interconverting a single substrate and a single product. Using the enediol intermediate of the reaction (which allowed solvent protons to enter the reaction from the middle instead of only from the substrate or product) and kinetic isotope effects, he measured the relative free energy of each intermediate and transition state, which allowed him to depict the first free energy profile for an enzyme-catalyzed reaction. This work was done with his long-term collaborator, John Albery. His profile showed that TIM was a "perfect" enzyme in that catalysis is limited only by the rate of diffusion. Later, Knowles applied similar methods to proline racemase, developing an elegant method to discern whether a reaction proceeds via a stepwise or concerted manner and discovering the consequences of "oversaturation", a situation in which the interconversion of unliganded forms of the enzyme limit catalysis.

At Harvard, Knowles also did important work on β-lactamases and their mechanism-based inhibitors. And, he provided key insight on the stereochemistry of phosphoryl group transfer reactions, using synthetic phosphoryl groups containing 16O, 17O, and 18O isotopes.

Knowles was the author of more than 250 research papers, and advised more than 50 Ph.D. recipients at Oxford and at Harvard, including Hagan Bayley, Stephen L. Buchwald, and Ronald T. Raines.

Awards and honours[edit]

Knowles was a Fellow of the Royal Society, the American Academy of Arts and Sciences, the American Philosophical Society, the American Association for the Advancement of Science, and a Foreign Associate of the National Academy of Sciences. Among his awards are the Royal Society of Chemistry's Charmian Medal, the Bader Award, the Repligen Corporation Award in Chemistry of Biological Processes, the Prelog Medal, the Robert A. Welch Award in Chemistry, the Arthur C. Cope Scholar Award, and the Nakanishi Prize. He was awarded the Davy Medal of the Royal Society, and was an Honorary Fellow of Balliol College and of Wadham College, Oxford. He held honorary degrees from the University of Edinburgh and the Eidgenössische Technische Hochschule in Zürich. He was appointed CBE in the Queen's Birthday Honours of 1993. He was elected one of nine Trustees of the Howard Hughes Medical Institute in 1998.

Royal Society of Chemistry – Jeremy Knowles Award (2014)

The Royal Society of Chemistry awards a 'Jeremy Knowles Award', " to recognise and promote the importance of inter- and multi-disciplinary research between chemistry and the life sciences".[4]

References[edit]

  1. ^ Bayley, H.; Knowles, J. R. (1978). "Photogenerated reagents for membrane labeling. 2. Phenylcarbene and adamantylidene formed within the lipid bilayer". Biochemistry. 17 (12): 2420–2423. doi:10.1021/bi00605a026. PMID 678520.
  2. ^ Raines, R. T. (2008). "Jeremy R. Knowles (1935–2008)". ACS Chemical Biology. 3 (5): 262–264. doi:10.1021/cb800099n. PMID 18484705.
  3. ^ Jeremy R. Knowles named Interim Dean of the Faculty of Arts and Sciences, Harvard University Gazette, published 2006-05-22. Retrieved 2009-06-10.
  4. ^ "RSC Jeremy Knowles Award". Royal Society of Chemistry. Retrieved 2014-11-14.

External links[edit]