Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996) and continued his career at the Karolinska Institute as a postdoctoral scientist (1996-1999). In 1999, he joined the Pharmacia Corporation as a principal research scientist in structural biology and biophysics. He left the company in 2004 to set up a research group at the Structural Genomics Consortium at Oxford University (SGC). From 2008 to 2015 he was a Professor of Structural Biology at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and between 2012 and 2015 he was the Director for Chemical Biology at the Target Discovery Institute (TDI). He joined Frankfurt University (Germany) in 2015 as a Professor of Pharmaceutical Chemistry and the Buchmann Institute of Molecular Life Sciences. He remains associated to the SGC as a visiting Professor at Oxford and he is also adjunct Professor of the George Washington University. Since 2017 he is the CSO of the newly founded SGC node at the Goethe-University Frankfurt. His research interests are the rational design of selective inhibitors that target protein kinases as well as protein interactions modules that function as reader domains of the epigenetic code.
My laboratory is interested in understanding molecular mechanisms that regulate protein function of key signalling molecules and how these mechanisms can be utilized for the development of highly selective and potent inhibitors (chemical probes). As a basis for this work we have generated a comprehensive set of high resolution crystal structures that cover most members of the protein family of interest. We are particularly interested in protein interactions module of the bromodomain family that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. This effort generated several highly selective chemical probes targeting bromodomains. A second research focus is on protein kinases. Our laboratory has solved a comprehensive set of crystal structure of this large protein family offering the opportunity to understand molecular mechanisms of their regulation and developing new strategies for their selective targeting. We developed for example a number of highly selective inhibitors by exploring unusual binding modes and allosteric binding sites. A particular focus of the laboratory is also to understand structural mechanisms leading to slow binding kinetics as part of the K4DD consortium.
Tuppi M, Kehrloesser S, Coutandin DW, Rossi V, Luh LM, Strubel A, Hötte K, Hoffmeister M, Schäfer B, De Oliveira T, Greten F, Stelzer EHK, Knapp S, De Felici M, Behrends C, Klinger FG, Dötsch V
Nat. Struct. Mol. Biol.. 2018-2-26 . .doi: 10.1038/s41594-018-0035-7
PMID: 29483652Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, Masuda K, Karaminejadranjbar M, Mannion D, Miranda F, Herrero-Gonzalez S, Hellner K, Chen F, Alsaadi A, Albukhari A, Fotso DC, Yau C, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Knapp S, Gray NS, Campo L, Myers KA, Dhar S, Ferguson D, Bast RC, Sood AK, von Delft F, Ahmed AA
Nat Commun. 2018-2-2 . 9(1):476 .doi: 10.1038/s41467-017-02811-7
PMID: 29396402Schrade K, Tröger J, Eldahshan A, Zühlke K, Abdul Azeez KR, Elkins JM, Neuenschwander M, Oder A, Elkewedi M, Jaksch S, Andrae K, Li J, Fernandes J, Müller PM, Grunwald S, Marino SF, Vukićević T, Eichhorst J, Wiesner B, Weber M, Kapiloff M, Rocks O, Daumke O, Wieland T, Knapp S, von Kries JP, Klussmann E
PLoS ONE. 2018-1-27 . 13(1):e0191423 .doi: 10.1371/journal.pone.0191423
PMID: 29373579Vasta JD, Corona CR, Wilkinson J, Zimprich CA, Hartnett JR, Ingold MR, Zimmerman K, Machleidt T, Kirkland TA, Huwiler KG, Ohana RF, Slater M, Otto P, Cong M, Wells CI, Berger BT, Hanke T, Glas C, Ding K, Drewry DH, Huber KVM, Willson TM, Knapp S, Müller S, Meisenheimer PL, Fan F, Wood KV, Robers MB
Cell Chem Biol. 2017-11-13 . .doi: 10.1016/j.chembiol.2017.10.010
PMID: 29174542Shadrick WR, Slavish PJ, Chai SC, Waddell B, Connelly M, Low JA, Tallant C, Young BM, Bharatham N, Knapp S, Boyd VA, Morfouace M, Roussel MF, Chen T, Lee RE, Kiplin Guy R, Shelat AA, Potter PM
Bioorg. Med. Chem.. 2017-11-4 . .doi: 10.1016/j.bmc.2017.10.042
PMID: 29170024Schuller M, Riedel K, Gibbs-Seymour I, Uth K, Sieg C, Gehring AP, Ahel I, Bracher F, Kessler BM, Elkins JM, Knapp S
ACS Chem. Biol.. 2017-10-9 . .doi: 10.1021/acschembio.7b00445
PMID: 28991428Wang BD, Ceniccola K, Hwang S, Andrawis R, Horvath A, Freedman JA, Olender J, Knapp S, Ching T, Garmire L, Patel V, Garcia-Blanco MA, Patierno SR, Lee NH
Nat Commun. 2017-9-27 . 8:16161 .doi: 10.1038/ncomms16161
PMID: 28952599Meier JC, Tallant C, Fedorov O, Witwicka H, Hwang SY, van Stiphout RG, Lambert JP, Rogers C, Yapp C, Gerstenberger BS, Fedele V, Savitsky P, Heidenreich D, Daniels DL, Owen DR, Fish PV, Igoe NM, Bayle ED, Haendler B, Oppermann UCT, Buffa F, Brennan PE, Müller S, Gingras AC, Odgren PR, Birnbaum MJ, Knapp S
ACS Chem. Biol.. 2017-8-29 . .doi: 10.1021/acschembio.7b00481
PMID: 28849908Ferguson FM, Doctor ZM, Chaikuad A, Sim T, Kim ND, Knapp S, Gray NS
Bioorg. Med. Chem. Lett.. 2017-8-10 . .doi: 10.1016/j.bmcl.2017.08.016
PMID: 28818446Aldeghi M, Bodkin MJ, Knapp S, Biggin PC
J Chem Inf Model. 2017-8-8 . .doi: 10.1021/acs.jcim.7b00347
PMID: 28786670