Charles Craik

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Charles Craik

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Professor, School of Pharmacy
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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.
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  1. Singh A, Shenai BR, Choe Y, Gut J, Sijwali PS, Craik CS, Rosenthal PJ. Critical role of amino acid 23 in mediating activity and specificity of vinckepain-2, a papain-family cysteine protease of rodent malaria parasites. Biochem J. 2002 Nov 15; 368(Pt 1):273-81.
  2. Wang X, Choe Y, Craik CS, Ellman JA. Design and synthesis of novel inhibitors of gelatinase B. Bioorg Med Chem Lett. 2002 Aug 19; 12(16):2201-4.
  3. Lecaille F, Choe Y, Brandt W, Li Z, Craik CS, Brömme D. Selective inhibition of the collagenolytic activity of human cathepsin K by altering its S2 subsite specificity. Biochemistry. 2002 Jul 02; 41(26):8447-54.
  4. Salter JP, Choe Y, Albrecht H, Franklin C, Lim KC, Craik CS, McKerrow JH. Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomes. J Biol Chem. 2002 Jul 05; 277(27):24618-24.
  5. Mathieu MA, Bogyo M, Caffrey CR, Choe Y, Lee J, Chapman H, Sajid M, Craik CS, McKerrow JH. Substrate specificity of schistosome versus human legumain determined by P1-P3 peptide libraries. Mol Biochem Parasitol. 2002 Apr 30; 121(1):99-105.
  6. Laboissière MC, Young MM, Pinho RG, Todd S, Fletterick RJ, Kuntz I, Craik CS. Computer-assisted mutagenesis of ecotin to engineer its secondary binding site for urokinase inhibition. J Biol Chem. 2002 Jul 19; 277(29):26623-31.
  7. Reiling KK, Endres NF, Dauber DS, Craik CS, Stroud RM. Anisotropic dynamics of the JE-2147-HIV protease complex: drug resistance and thermodynamic binding mode examined in a 1.09 A structure. Biochemistry. 2002 Apr 09; 41(14):4582-94.
  8. Wang B, Brown KC, Lodder M, Craik CS, Hecht SM. Chemically mediated site-specific proteolysis. Alteration of protein-protein interaction. Biochemistry. 2002 Feb 26; 41(8):2805-13.
  9. Maly DJ, Leonetti F, Backes BJ, Dauber DS, Harris JL, Craik CS, Ellman JA. Expedient solid-phase synthesis of fluorogenic protease substrates using the 7-amino-4-carbamoylmethylcoumarin (ACC) fluorophore. J Org Chem. 2002 Feb 08; 67(3):910-5.
  10. C.S. Craik & R.J. Fletterick. The Marriage of Protein Structure and Pharmaceutical Discovery. Biotech. & Appl. Biochem. 26 . 1997; 125-126 .
  11. Dauber DS, Ziermann R, Parkin N, Maly DJ, Mahrus S, Harris JL, Ellman JA, Petropoulos C, Craik CS. Altered substrate specificity of drug-resistant human immunodeficiency virus type 1 protease. J Virol. 2002 Feb; 76(3):1359-68.
  12. Todd S, Laboissière MC, Craik CS. Yeast two-hybrid assay for examining human immunodeficiency virus protease heterodimer formation with dominant-negative inhibitors and multidrug-resistant variants. Anal Biochem. 2000 Jan 15; 277(2):247-53.
  13. B. Wang, M. Lodder, J. Zhou, T.T. Baird, Jr., K.C. Brown, C.S. Craik, S.M. Hecht. J. Am. Chem. Soc. Chemically Mediated Site-Specific Cleavage of Proteins. 2000; 122:7402-7403.
  14. K.K. Reiling, T.R. Pray, C.S. Craik, R.M. Stroud. Structure: Regulation of Activity and Dimerization by Conserved Structural Elements. Biochemistry. 2000; 24:12796-803 .
  15. T.T. Baird Jr., B. Wang, M. Lodder, S.M. Hecht and C.S. Craik. Generation of Active Trypsin by Chemical Cleavage. Tetrahedron Letters. 2000; 556:9477-9485 .
  16. C.S. Craik & R.J. Fletterick. The Marriage of Protein Structure and Pharmaceutical Discovery. Biotech. & Appl. Biochem. 26 . 1997; 125-126 .
  17. 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. 1996; 1545-1558 .
  18. 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. 1995; 29:1501S-1517S.
  19. 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. 1996; 1545-1558 .
  20. 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 . 1996; 1421-1427.
  21. S. Halfon & C.S. Craik. Regulation of Proteolytic Activity by Engineered Tridentate Metal Binding Loops. J. Am. Chem. Soc. 118. 1996; 1227-1228 .
  22. W.S. Willett, L.S. Brinen, R.J. Fletterick & C.S. Craik. Delocalizing Trypsin Specificity with Metal-Activation. Biochem; 35. 1996; 5992-5998.
  23. 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. 1996; 5846-5856.
  24. 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. . J. Bio. Chem. Structure of a Non-Peptide Inhibitor Complexed with HIV-1 Protease: Developing a Cycle of Structure-Based Drug Design. 1993; 15343-15346.
  25. Z. Sui, J. DeVoss, D. DeCamp, J. Li, C.S. Craik & P.R. Ortiz de Montellano. Synthesis. Synthesis of Haloperidol Ethanedithioketal HIV-1 Protease Inhibitors: Magnesium Chloride Facilitated Addition of Grignard Reagents. 1993; 8:803-808.