{{Short description|British chemist (1935–2008)}} {{Use British English|date=August 2017}} {{Use dmy dates|date=August 2017}} {{Infobox scientist | name = Jeremy Knowles | honorific_suffix = {{post-nominals|country=GBR|CBE|FRS|size=100%}} | birth_name = Jeremy Randall Knowles | image = | image_size = | caption = | birth_date = {{birth date|df=yes|1935|04|28}} | birth_place = [[Rugby, Warwickshire|Rugby]], England<ref>{{cite web | url = https://news.harvard.edu/gazette/story/2009/05/jeremy-randall-knowles/ | title = Jeremy Randall Knowles| date = 14 May 2009}}</ref> | death_date = {{Death date and age|df=yes|2008|04|03|1935|04|28}} | death_place = [[Cambridge, Massachusetts]]<ref name = acschembiol /> | field = [[Biochemistry]] | academic_advisors = [[Richard Norman (chemist)|Richard Norman]], [[George S. Hammond]] | work_institutions = [[Oxford University]]<br/> [[Harvard University]]<br/>[[California Institute of Technology]] | education = [[Balliol College, Oxford]] ([[Bachelor of Arts|BA]])<br>[[Merton College, Oxford]] ([[DPhil]]) | doctoral_advisor = | doctoral_students = {{Plainlist| * [[Hagan Bayley]]<ref>{{Cite journal | last1 = Bayley | first1 = H. | authorlink1 = Hagan Bayley | last2 = Knowles | first2 = J. R. | authorlink2 = Jeremy R. Knowles | title = Photogenerated reagents for membrane labeling. 2. Phenylcarbene and adamantylidene formed within the lipid bilayer | journal = Biochemistry | volume = 17 | issue = 12 | pages = 2420–2423 | year = 1978 | pmid = 678520 | doi=10.1021/bi00605a026 }}</ref> * [[Stephen L. Buchwald]]<ref>{{cite journal |doi=10.1021/ja00369a055|title=Nucleophilic displacements on phosphoric monoesters: Stereochemical evidence|year=1982|last1=Buchwald|first1=Stephen L.|last2=Knowles|first2=Jeremy R.|journal=Journal of the American Chemical Society|volume=104|issue=5|pages=1438–1440|bibcode=1982JAChS.104.1438B }}</ref> * [[Athel Cornish-Bowden]]<ref name="pepsin">{{cite journal |doi=10.1042/bj1130353|title=The pH-dependence of pepsin-catalysed reactions|year=1969|last1=Cornish-Bowden|first1=A. J.|last2=Knowles|first2=J. R.|journal=Biochemical Journal|volume=113|issue=2|pages=353–362|pmid=4897198|pmc=1184642}}</ref> * [[Ronald T. Raines]]<ref>{{cite journal |doi=10.1021/bi00396a024|title=Enzyme relaxation in the reaction catalyzed by triosephosphate isomerase: Detection and kinetic characterization of two unliganded forms of the enzyme|year=1987|last1=Raines|first1=Ronald T.|last2=Knowles|first2=Jeremy R.|journal=Biochemistry|volume=26|issue=22|pages=7014–7020|pmid=3427057}}</ref>}} | thesis_url = https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.710173 | thesis_title = Intramolecular effects in aromatic systems | thesis_year = 1961 | known_for = [[Enzyme catalysis]] | notable_students = [[Lia Addadi]]<ref>{{cite journal | doi= 10.1021/bi00288a022| title= Secondary tritium isotope effects as probes of the enzymic and nonenzymic conversion of chorismate to prephenate| year= 1983| last1= Addadi| first1= Lia| last2= Jaffe| first2= Eileen K.| last3= Knowles| first3= Jeremy R.| journal= Biochemistry| volume= 22| issue= 19| pages= 4494–4501| pmid= 6354259}}</ref> | prizes = [[Welch Award in Chemistry]] {{small|(1995)}}<br>[[Nakanishi Prize]] {{small|(1999)}} | footnotes = | signature = }}
'''Jeremy Randall Knowles''' {{post-nominals|country=GBR|CBE|FRS}} (28 April 1935 – 3 April 2008) was a professor of chemistry at [[Harvard University]] who served as [[Dean (education)|dean]] of the Harvard University faculty of arts and sciences (FAS) from 1991 to 2002.<ref>[http://news.harvard.edu/specials/2002/knowles/ Bio from Harvard] (from the office of news and public affairs)</ref><ref>{{Cite web |url=http://www.wnyc.org/legacy/shows/madaboutmusic/Knowlesbio.html |title=Public biography |access-date=20 December 2005 |archive-date=30 December 2004 |archive-url=https://web.archive.org/web/20041230184223/http://www.wnyc.org/legacy/shows/madaboutmusic/Knowlesbio.html |url-status=dead }}</ref><ref>[http://www.thecrimson.com/article.aspx?ref=152058 Harvard Crimson Profile]</ref> 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.<ref name = acschembiol>{{Cite journal | last1 = Raines | first1 = R. T. | title = Jeremy R. Knowles (1935–2008) | doi = 10.1021/cb800099n | journal = ACS Chemical Biology | volume = 3 | issue = 5 | pages = 262–264 | year = 2008 | pmid = 18484705 }}</ref>
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]].<ref>[http://www.news.harvard.edu/gazette/daily/2006/05/22-fasdean.html Jeremy R. Knowles named Interim Dean of the Faculty of Arts and Sciences] {{Webarchive|url=https://web.archive.org/web/20080517011934/http://www.news.harvard.edu/gazette/daily/2006/05/22-fasdean.html |date=17 May 2008 }}, Harvard University Gazette, published 2006-05-22. Retrieved 2009-06-10.</ref><ref>{{Cite web |url=http://www.news.harvard.edu/gazette/2008/04.03/99-knowles.html |title=Harvard Gazette Obituary |access-date=4 April 2008 |archive-url=https://web.archive.org/web/20080511181456/http://www.news.harvard.edu/gazette/2008/04.03/99-knowles.html |archive-date=11 May 2008 |url-status=dead }}</ref><ref>[https://web.archive.org/web/20080413004644/http://www.telegraph.co.uk/news/main.jhtml?view=DETAILS&grid=&xml=/news/2008/04/09/db0902.xml Daily Telegraph Obituary]</ref>
==Biography== Knowles was born in England in 1935, educated at [[Magdalen College School, Oxford]], [[Balliol College, Oxford]] ([[Bachelor of Arts|BA]] 1958, first class degree in Chemistry 1959), and [[Merton College, Oxford]] ([[Doctor of Philosophy|DPhil]] 1961).<ref name="MCreg">{{cite book|editor1-last=Levens|editor1-first=R.G.C.|title=Merton College Register 1900-1964|date=1964|publisher=Basil Blackwell|location=Oxford|page=511}}</ref><ref name=aphd>{{cite thesis|degree=DPhil|publisher=University of Oxford|url=https://copac.jisc.ac.uk/id/40893512?style=html|title=Intramolecular effects in aromatic systems|first=Jeremy|last=Knowles|date=1961|id={{EThOS|uk.bl.ethos.710173}}|website=jisc.ac.uk|oclc=275990698}}{{Dead link|date=October 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><!-- Oxford uses the abbreviation DPhil, not PhD. --> He was a [[Pilot Officer]] in the [[Royal Air Force]]. During his undergraduate he did research in [[Richard Norman (chemist)|Richard Norman]]'s physical organic chemistry laboratory. There, he studied electronic effects on the rates of aromatic substitution reactions.<ref>{{cite journal | doi= 10.1039/jr9600004885 | journal = J. Chem. Soc. | pages= 4885–4896 | year = 1960 |author1=Knowles, J R |author2=Norman, R O C |author3=Radda, G K | title = A quantitative treatment of electrophilic aromatic substitution}}</ref> In 1960, he became a University Lecturer at Oxford, and Fellow of [[Wadham College, Oxford]].
==Career and research== In 1961, he took a post-doctoral fellowship at the [[California Institute of Technology]], working with [[George S. Hammond]], who was an organic [[photochemistry|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'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]]<ref>{{cite journal | doi= 10.1042/bj1040369| title= Specificity and stereospecificity of α-chymotrypsin| year= 1967| last1= Ingles| first1= DW| last2= Knowles| first2= JR| journal= Biochemical Journal| volume= 104| issue= 2| pages= 369–377| pmid= 6048779| pmc= 1270596}}</ref> and [[pepsin]],<ref name="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.<ref>{{cite journal | doi= 10.1021/ar50052a006| title= Photogenerated reagents for biological receptor-site labeling| year= 1972| last1= Knowles| first1= Jeremy R.| journal= Accounts of Chemical Research| volume= 5| issue= 4| pages= 155–160}}</ref>
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]].<ref>{{cite journal | doi= 10.1002/anie.197702851| title= Efficiency and Evolution of Enzyme Catalysis| year= 1977| last1= Albery| first1= W. John| last2= Knowles| first2= Jeremy R.| journal= Angewandte Chemie International Edition in English| volume= 16| issue= 5| pages= 285–293| pmid= 406815}}</ref> 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,<ref>{{cite journal | doi= 10.1021/bi00357a037| title= Energetics of proline racemase: Racemization of unlabeled proline in the unsaturated, saturated, and oversaturated regimes| year= 1986| last1= Fisher| first1= L. Mark| last2= Albery| first2= W. John| last3= Knowles| first3= Jeremy R.| journal= Biochemistry| volume= 25| issue= 9| pages= 2529–2537| pmid= 3755058}}</ref> 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 <sup>16</sup>O, <sup>17</sup>O, and <sup>18</sup>O isotopes.<ref>{{cite journal | doi= 10.1038/275564a0| title= Stereochemistry of phosphoryl group transfer using a chiral [16O, 17O, 18O] stereochemical course of alkaline phosphatase| year= 1978| last1= Jones| first1= Stephen R.| last2= Kindman| first2= L. Allen| last3= Knowles| first3= Jeremy R.| journal= Nature| volume= 275| issue= 5680| pages= 564–565| pmid= 357996| bibcode= 1978Natur.275..564J| s2cid= 4203653}}</ref>
Knowles was the author of more than 250 research papers, and advised many doctoral students and post-doctoral researchers<ref>{{cite web | url = https://academictree.org/chemistry/tree.php?pid=32641 | title = Chemistry tree | access-date = 3 April 2021}}</ref> at Oxford and at Harvard, including [[Hagan Bayley]], [[Stephen L. Buchwald]], [[Athel Cornish-Bowden]], [[Andreas Plückthun]], and [[Ronald T. Raines]].
===Awards and honours=== Knowles was elected a [[Fellow of the Royal Society]] (FRS),{{when|date=May 2019}} a [[Fellow of the American Academy of Arts and Sciences]] (FAAAS) in 1982,<ref>{{Cite web |title=Jeremy Randall Knowles |url=https://www.amacad.org/person/jeremy-randall-knowles |access-date=2022-05-02 |website=American Academy of Arts & Sciences |language=en}}</ref> and member of [[American Philosophical Society]] in 1988,<ref>{{Cite web |title=APS Member History |url=https://search.amphilsoc.org/memhist/search?creator=Jeremy+R.+Knowles&title=&subject=&subdiv=&mem=&year=&year-max=&dead=&keyword=&smode=advanced |access-date=2022-05-02 |website=search.amphilsoc.org}}</ref> the [[American Association for the Advancement of Science]], and a [[Foreign Associate of the National Academy of Sciences]].<ref>{{Cite web |title=Jeremy R. Knowles |url=http://www.nasonline.org/member-directory/deceased-members/8887.html |access-date=2022-05-02 |website=www.nasonline.org}}</ref> 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 [[ETH Zurich|Eidgenössische Technische Hochschule]] in [[Zürich]]. He was appointed [[Order of the British Empire]] in the [[1993 Birthday Honours]]. He was elected one of nine Trustees of the [[Howard Hughes Medical Institute]] in 1998.<ref>*[http://www.hhmi.org/news/knowles.html HHMI bio] {{Webarchive|url=https://web.archive.org/web/20051123150856/http://www.hhmi.org/news/knowles.html |date=23 November 2005 }}</ref>
[[File:Royal Society of Chemistry - Jeremy Knowles Award - 2014 - Andy Mabbett - 01.JPG|thumb|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".<ref name="RSC">{{cite web|url=http://www.rsc.org/ScienceAndTechnology/Awards/JeremyKnowlesAward/|title=RSC Jeremy Knowles Award|publisher=[[Royal Society of Chemistry]]|access-date=2014-11-14}}</ref>
==Personal life== Knowles married Jane Sheldon Davis in 1960, and together they had three sons.<ref name="MCreg" />
==References== {{Reflist}}
{{Authority control}} {{Repligen Corporation Award in Chemistry of Biological Processes}}
{{DEFAULTSORT:Knowles, Jeremy}} [[Category:1935 births]] [[Category:2008 deaths]] [[Category:British chemists]] [[Category:Fellows of the Royal Society]] [[Category:Fellows of the American Academy of Arts and Sciences]] [[Category:Foreign associates of the National Academy of Sciences]] [[Category:People educated at Magdalen College School, Oxford]] [[Category:Alumni of Balliol College, Oxford]] [[Category:Fellows of Balliol College, Oxford]] [[Category:Harvard University faculty]] [[Category:Commanders of the Order of the British Empire]] [[Category:Royal Air Force officers]] [[Category:Alumni of Merton College, Oxford]] [[Category:Members of the American Philosophical Society]] [[Category:Chemists of the University of Oxford]]