Charles Craik, PhD

charles.jpg
Professor
P_Pharmaceutical Chemistry
+1 415 476-8146

My research interests focus on defining the roles and the mechanisms of enzymes and other challenging proteins in complex biological processes and on developing technologies to facilitate these studies. The current research in the Craik lab focuses on the chemical biology of proteolytic and protein degradation enzymes, receptors and membrane transporters. A particular emphasis of our work is on identifying the roles and regulating the activity of key proteins associated with infectious diseases, neurodegeneration and cancer. I am also interested in developing novel methods to biophysically characterize challenging proteins as well as their complexes. These studies coupled with our global substrate profiling, antibody engineering and noninvasive imaging efforts are providing a better understanding of both the chemical make-up and the biological importance of these critical proteins to aid in the rapid detection, monitoring and control of infectious disease, neurological disorders and cancer. This in turn is leading to the development of strategies for regulating these activities as a means of therapeutic intervention. Further study of these proteins holds promise for better understanding, rapid detection and eventual control of infectious diseases, cancer and neurodegeneration.

Publications

Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy.

Science advances

Detomasi TC, Degotte G, Huang S, Suryawanshi RK, Diallo A, Lizzadro L, Zaptero-Belinchón FJ, Taha TY, Li J, Richards AL, Hantz ER, Alam Z, Montano M, McCavitt-Malvido M, Gumpena R, Partridge JR, Correy GJ, Matsui Y, Charvat AF, Glenn IS, Rosecrans J, Revalde JL, Anderson D, Hultquist JF, Arkin MR, Neitz RJ, Swaney DL, Krogan NJ, Shoichet BK, Verba KA, Ott M, Renslo AR, Craik CS

Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors.

Protein science : a publication of the Protein Society

Fink EA, Bardine C, Gahbauer S, Singh I, Detomasi T, White K, Gu S, Wan X, Chen J, Ary B, Glenn I, O'Connell J, O'Donnell H, Fajtová P, Lyu J, Vigneron S, Young NJ, Kondratov IS, Alisoltani A, Simons LM, Lorenzo-Redondo R, Ozer EA, Hultquist JF, O'Donoghue AJ, Moroz Y, Taunton J, Renslo AR, Irwin JJ, García-Sastre A, Shoichet BK, Craik CS

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

Nature

Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.

bioRxiv : the preprint server for biology

Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, O'Meara MJ, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Naing ZZC, Zhou Y, Peng S, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Shen W, Shi Y, Zhang Z, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Ramachandran R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Lin Y, Wankowicz SA, Bohn M, Trenker R, Young JM, Cavero D, Hiatt J, Roth T, Rathore U, Subramanian A, Noack J, Hubert M, Roesch F, Vallet T, Meyer B, White KM, Miorin L, Agard D, Emerman M, Ruggero D, García-Sastre A, Jura N, von Zastrow M, Taunton J, Schwartz O, Vignuzzi M, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor S, Fraser JS, Gross J, Sali A, Kortemme T, Beltrao P, Shokat K, Shoichet BK, Krogan NJ

Imaging PD-L1 Expression with ImmunoPET.

Bioconjugate chemistry

Truillet C, Oh HLJ, Yeo SP, Lee CY, Huynh LT, Wei J, Parker MFL, Blakely C, Sevillano N, Wang YH, Shen YS, Olivas V, Jami KM, Moroz A, Jego B, Jaumain E, Fong L, Craik CS, Chang AJ, Bivona TG, Wang CI, Evans MJ

Global landscape of HIV-human protein complexes.

Nature

Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K, Hernandez H, Jang GM, Roth SL, Akiva E, Marlett J, Stephens M, D'Orso I, Fernandes J, Fahey M, Mahon C, O'Donoghue AJ, Todorovic A, Morris JH, Maltby DA, Alber T, Cagney G, Bushman FD, Young JA, Chanda SK, Sundquist WI, Kortemme T, Hernandez RD, Craik CS, Burlingame A, Sali A, Frankel AD, Krogan NJ

Untitled Publication

Shimba, N. Nomura, A.M., Marnett, A.B. and Craik, C.S. Herpesvirus Protease Inhibition by Dimer Disruption. J. Virol

J. Am. Chem. Soc

Chemically Mediated Site-Specific Cleavage of Proteins

B. Wang, M. Lodder, J. Zhou, T.T. Baird, Jr., K.C. Brown, C.S. Craik, S.M. Hecht

Untitled Publication

K.K. Reiling, T.R. Pray, C.S. Craik, R.M. Stroud. Structure: Regulation of Activity and Dimerization by Conserved Structural Elements. Biochemistry

Untitled Publication

T.T. Baird Jr., B. Wang, M. Lodder, S.M. Hecht and C.S. Craik. Generation of Active Trypsin by Chemical Cleavage. Tetrahedron Letters

Untitled Publication

C.S. Craik & R.J. Fletterick. The Marriage of Protein Structure and Pharmaceutical Discovery. Biotech. & Appl. Biochem. 26

Untitled Publication

E.E. Rutenber, F. McPhee, A.P. Kaplan, S.L. Gallion, J.C. Hogan Jr., C.S. Craik & R.M. Stroud. A New Class of HIV1 Protease Inhibitor: The Crystallographic Structure, Inhibition and Chemical Synthesis of an Aminimide Peptide Isostere. Bioorg.& Med. Chem. 4

Untitled Publication

R. Li, X. Chen, B. Gong, Z. Li, E. Davidson, G. Kurzban, R.E. Miller, E.O. Nuzman, J.H. McKerrow, R.J. Fletterick, S.A. Gillmore, C.S. Craik, I.D. Kuntz, F.E. Cohen & G.L. Kenyon. Structure-based Design of Parasitic Protease Inhibitors. Bioorg. & Med. Chem. 4

Untitled Publication

S. Halfon & C.S. Craik. Regulation of Proteolytic Activity by Engineered Tridentate Metal Binding Loops. J. Am. Chem. Soc. 118

Untitled Publication

W.S. Willett, L.S. Brinen, R.J. Fletterick & C.S. Craik. Delocalizing Trypsin Specificity with Metal-Activation. Biochem; 35

Untitled Publication

Z. Yu, P. Caldera, F. McPhee, J. DeVoss, P.R. Jones, A. Burlingame, I. Kuntz, C.S. Craik & P.R. Ortiz de Montellano. Irreversible Inhibition of the HIV-1 Protease: Targeting Alkylating Agents to the Catalytic Aspartate Groups. J. Amer. Chem. Soc. 118

Untitled Publication

A.E. Eakin, J.H. McKerrow & C.S.Craik. A Cysteine Protease is a Target for the Enzyme Structure-based Design of Antiparasitic Drugs. Drug Information Journal 29

Untitled Publication

K.L. Lee, F. McPhee, J.J. DeVoss, C.S. Craik & P. Ortiz de Montellano. Nonpeptide HIV Protease Inhibitors. Differential Introduction of Alkylamino Groups into the two Aryl Rings of Haloperidol. J. of Organic Chemistry 59

J. Bio. Chem

Structure of a Non-Peptide Inhibitor Complexed with HIV-1 Protease: Developing a Cycle of Structure-Based Drug Design

E. Rutenber, E.B. Fauman, R.J. Keenan, S. Fong, P.S. Furth, P.R. Ortiz de Montellano, E. Meng, I.D. Kuntz, D.L. DeCamp, R. Salto, J.R. Rosé, C.S. Craik, R.M. Stroud.

Synthesis

Synthesis of Haloperidol Ethanedithioketal HIV-1 Protease Inhibitors: Magnesium Chloride Facilitated Addition of Grignard Reagents

Z. Sui, J. DeVoss, D. DeCamp, J. Li, C.S. Craik & P.R. Ortiz de Montellano

Untitled Publication

D.L. Decamp, S.B. Kahl & C.S. Craik. Boronated Porphyrins—A New Class of HIV Proteinase Inhibitors. Intl. Antiviral News 1

Untitled Publication

J.J. Perona, C.A. Tsu, M.E. McGrath, C.S. Craik & R.J. Fletterick. Relocating a Negative Charge in the Binding Pocket of Trypsin. J. Mol. Bio. 230

Untitled Publication

T.K. Sawyer, J.F. Fisher, J.B. Hester, C.W. Smith, A.G. Tomasselli, W.G. Tarpley, P.S. Burton, J.O. Hui T.J. McQuade, R.A. Conradi, V.S. Bradford, L. Liu, J.H. Kinner, J.Tustin,D.L. Alexander, A.W. Harrison, D.E. Emmert, D.J. Staples, L.I. Maggira, Y.Z. Zhang, R.A. Poorman, BM. Dunn, C. Rao, .E. Scarborough, W.T. Lowther, C.S. Craik, D. DeCamp, J.Moon, W.H. Howe & R.L. Heinrikson. Peptidomimetic Inhibitors of Human Immunodeficiency Virus Protease (HIV-PR): Design, Enzyme Binding and Selectivity, Antiviral Efficacy and Cell Permeability Properties. Bioorg. Med. Chem. Letts 3

Untitled Publication

Z. Sui, R. Salto, C.S. Craik, P. Ortiz de Montellano. Inhibition of the HIV1 and the HIV2 Proteases by Curcumin and Curcumin Boron Complexes. Bioorg. & Med. Chem. Let. 1

Int. J. Pep. Protein Res

HIV Protease (HIV PR) Inhibitor Structure-Activity-Selectivity and Active Site Molecular Modeling of High Affinity Leu [CH(OH)CH2] Val Modified Viral and Nonviral Substrate Analogs

T.K. Sawyer, D.J. Staples, L. Liu, A.G. Tomasselli, J.O. Hui, K. O’Connell, H. Schostarez, J.B. Hester, J. Moon, W.J. Howe, C.W. Smith, D. L. DeCamp, C.S. Craik, B.M. Dunn,W. T. Lowther, J. Harris, R.A. Poorman, A. Wlodawer, M. Jaskolski & R.L. Heinrikson.

Untitled Publication

D.R. Corey, M.E. McGrath, J.R. Vasquez, R.J. Fletterick & C.S. Craik. An Alternate Geometry for the Catalytic Triad of Serine Proteases. J. Amer. Chem. Soc. 114

Adv. Exptl. Med. Bio

Structure-based inhibition of HIV-1 protease activity and viral infectivity

D.L. DeCamp, L.M. Babé, P. Furth, P. Ortiz de Montellano, I.D. Kuntz & C.S. Craik

Untitled Publication

L. Evnin, J. Vasquez & C.S. Craik. Proc. Substrate Specificity of Trypsin Investigated Using a Genetic Selection. Natl. Acad. Sci. USA 87

Untitled Publication

A.L. Ferris, A. Hizi, S.D. Showalter, S. Pichuantes, L. Babé & C.S. Craik. Immunologic and Proteolytic Analysis of HIV-2 Reverse Transcriptase Structure. Virology 175

Untitled Publication

E. Stewart, C.S. Craik, L. Hake & A. Bowcock. Human CPA Identifies a BglII RFLP and Maps to 7q31-qter. Amer. J. Hum. Gen. 46, 795 -800

Untitled Publication

M. Obukowicz, M. Gustafson, K. Junger, R. Leimgruber, A. Wittwer, T-C. Wun, T. Warren, B. Bishop, K. Mathis, D. McPherson, N. Siegel, M. Jennings, B. Brightwell, J. Diaz-Collier, L. Bell, C.S. Craik & W. Tacon. Secretion of Active Kringle 2-Serine Protease in E. coli. J. Bio. Chem. 29, 9737-9745

Untitled Publication

S. Pichuantes, L. Babé, P. Barr, D. DeCamp & C.S. Craik. Recombinant HIV 2 Protease Processes HIV 1 Pr53gag and Analogous Junction Peptides In Vitro. J. Bio. Chem. 265, 13890-13898

Untitled Publication

A. Eakin, J.N. Higaki, J.H. McKerrow & C.S. Craik. Cysteine or Serine Proteinase. Nature 342,132

Untitled Publication

J. Higaki L.B. Evnin & C.S. Craik. Introduction of a Cysteine Protease Active Site into Trypsin. Biochem. 28, 9256-9263

Untitled Publication

C.S. Craik, S. Roczniak, S. Sprang, R.J. Fletterick & W.J. Rutter. Edited by D. Cunningham and G. Long. New York: Alan R Liss, Inc. Redesigning Trypsin via Genetic Engineering. In: Proteases in Biological Control and Biotechnology

Untitled Publication

C.S. Craik. Edited by D. Oxender. New York: Alan R. Liss, Inc. Expression and Overproduction of Proteins. In: Protein Structure, Folding and Design 2, pp. 467-476.

Untitled Publication

T.L. Burgess, C.S. Craik, L. Matsuuchi & R.B. Kelly. In Vitro Mutagenesis of Trypsinogen: The Role of the N-Terminus in Intracellular Protein Targeting to Secretory Granules. J. Cell Bio. 105, 659-668

Untitled Publication

W.J. Rutter, S.J. Gardell, S. Roczniak, D. Hilvert, S. Sprang, R.J. Fletterick & C.S. Craik. Edited by D. Oxender and C.F. Fox. New York: Alan R. Liss, Inc. Redesigning Proteins via Genetic Engineering. In: Protein Modification and Design, pp. 257-267

Untitled Publication

S. Gardell, C.S. Craik, D. Hilvert, M. Urdea & W. Rutter. Edited by I. Bertini, C. Luchinat, W. Maret, and M. Zeppezauer. Boston, Massachusetts: Birkhäuser. Probing the Role of Tyrosine 248 in Carboxypeptidase A with Site-Directed Mutagenesis. In: Comparative Analysis of Catalytic Mechanisms of Zinc Enzymes.

Biotechniques

Use of Oligonucleotides for Site-Specific Mutagenesis

C.S. Craik

Untitled Publication

C.S. Craik & S. Beychok. Edited by C. Ho. In: Interaction Between Iron Proteins in Oxygen and Electron Transport, Elsevier North Holland Biomedical Press