chagas-Tcruzi 300x200Electron micrograph of the parasite Trypanosoma cruzi. Credit: Stephanie Hopkins & Juan Engel
 

Our research efforts have focused on both a basic biological understanding of the parasite and the disease, as well as efforts in drug discovery, including target identification, validation, screening, and lead optimization. Our most advanced program is focused on K777, an inhibitor of the cysteine protease, cruzain. We are working jointly with DNDi and the NIAID to complete IND-enabling studies for the K777-IND package.

Recent structural biology efforts have lent insight into requirements for cruzain inhibition, and our current efforts targeting cruzain are through development of backup leads to K777 and non-peptidyl inhibitors. Finally, new leads have been identified targeting CYP51, a key enzyme in the ergosterol synthetic pathway. Additional screening and chemical optimization of leads is in progress.

To expedite hit identification and lead characterization of novel anti-trypanosmal compounds, CDIPD scientists have developed a unique image-based whole-parasite screen. Several new collaborations have been initiated around this assay including an NIH funded program with the Genome Novartis Foundation focused on development of a novel clinical candidate for treatment of Chagas.

pipeline 720x38
 
  • FDA approved compounds, Stanford University
  • Novartis Genome Foundation/T. cruzi screening
  • CYP51 target-based screening
  • K777 analogs protease inhibitors
  • CYP51 inhibitors
 K777 IND-enabling

PUBLICATIONS

Rapid Chagas Disease Drug Target Discovery Using Directed Evolution in Drug-Sensitive Yeast. ACS Chem Biol. 2017 Feb 17;12(2):422-434. doi: 10.1021/acschembio.6b01037. Ottilie S, Goldgof GM, Calvet CM, Jennings GK, LaMonte G, Schenken J, Vigil E, Kumar P, McCall LI, Lopes ES, Gunawan F, Yang J, Suzuki Y, Siqueira-Neto JL, McKerrow JH, Amaro RE, Podust LM, Durrant JD, Winzeler EA.

Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1. Antimicrob Agents Chemother. 2015 May;59(5):2666-77. doi: 10.1128/AAC.04601-14. Epub 2015 Feb 23. Fonseca NC, da Cruz LF, da Silva Villela F, do Nascimento Pereira GA, de Siqueira-Neto JL, Kellar D, Suzuki BM, Ray D, de Souza TB, Alves RJ, Sales Júnior PA, Romanha AJ, Murta SM, McKerrow JH, Caffrey CR, de Oliveira RB, Ferreira RS.

Binding mode and potency of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors targeting Trypanosoma cruzi CYP51. J Med Chem. 2014 Dec 11;57(23):10162-75. doi: 10.1021/jm501568b. Epub 2014 Nov 25. Vieira DF, Choi JY, Calvet CM, Siqueira-Neto JL, Johnston JB, Kellar D, Gut J, Cameron MD, McKerrow JH, Roush WR, Podust LM.

Drug strategies targeting CYP51 in neglected tropical diseases. Chem Rev. 2014 Oct 22. [Epub ahead of print] No abstract available. Choi JY, Podust LM, Roush WR.

Lead identification to clinical candidate selection: drugs for Chagas disease. J Biomol Screen. 2015 Jan;20(1):101-11. doi: 10.1177/1087057114553103. Epub 2014 Oct 3. Neitz RJ, Chen S, Supek F, Yeh V, Kellar D, Gut J, Bryant C, Gallardo-Godoy A, Molteni V, Roach SL, Chatterjee AK, Robertson S, Renslo AR, Arkin M, Glynne R, McKerrow J, Siqueira-Neto JL.

4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency. J Med Chem. 2014 Aug 28;57(16):6989-7005. doi: 10.1021/jm500448u. Epub 2014 Aug 19. Calvet CM, Vieira DF, Choi JY, Kellar D, Cameron MD, Siqueira-Neto JL, Gut J, Johnston JB, Lin L, Khan S, McKerrow JH, Roush WR, Podust LM.

Determinants of disease phenotype in trypanosomatid parasites. Trends Parasitol. 2014 Jul;30(7):342-9. doi: 10.1016/j.pt.2014.05.001. Epub 2014 Jun 16. Review. McCall LI, McKerrow JH.

Diversity-oriented synthesis yields a new drug lead for treatment of Chagas disease. ACS Med Chem Lett. 2014 Feb 13;5(2):149-53. doi: 10.1021/ml400403u. Dandapani S, Germain AR, Jewett I, le Quement S, Marie JC, Muncipinto G, Duvall JR, Carmody LC, Perez JR, Engel JC, Gut J, Kellar D, Siqueira-Neto JL, McKerrow JH, Kaiser M, Rodriguez A, Palmer MA, Foley M, Schreiber SL, Munoz B.

R-Configuration of 4-aminopyridyl-based inhibitors of CYP51 confers superior efficacy against Trypanosoma cruzi. ACS Med Chem Lett. 2014 Apr 10;5(4):434-9. doi: 10.1021/ml500010m. Choi JY, Calvet CM, Vieira DF, Gunatilleke SS, Cameron MD, McKerrow JH, Podust LM, Roush WR.

Expanding the binding envelope of CYP51 inhibitors targeting Trypanosoma cruzi with 4-aminopyridyl-based sulfonamide derivatives. Chembiochem. 2014 May 26;15(8):1111-20. doi: 10.1002/cbic.201402027. Epub 2014 Apr 25. Vieira DF, Choi JY, Roush WR, Podust LM.

Identification of diversity-oriented synthesis derived small molecule, ML341, with cidal activity against Trypanosoma cruzi. 2012 Dec 17 [updated 2013 Nov 07]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Carmody LC, Germain AR, Engel JC, Gut J, Kaiser M, Jewett I, LeQuemen S, Marie JC, Dandapani S, Rodriguez A, Perez JR, McKerrow JH, Palmer MAJ, Munoz B, Schrieber SL.

Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma cruzi CYP51 as anti-chagas agents. J Med Chem. 2013 Oct 10;56(19):7651-68. doi: 10.1021/jm401067s. Epub 2013 Sep 30. Choi JY, Calvet CM, Gunatilleke SS, Ruiz C, Cameron MD, McKerrow JH, Podust LM, Roush WR.

Non-peptidic cruzain inhibitors with trypanocidal activity discovered by virtual screening and in vitro assay. PLoS Negl Trop Dis. 2013;7(8):e2370. doi: 10.1371/journal.pntd.0002370. Wiggers HJ, Rocha JR, Fernandes WB, Sesti-Costa R, Carneiro ZA, Cheleski J, da Silva AB, Juliano L, Cezari MH, Silva JS, McKerrow JH, Montanari CA.

Chemical-biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target. Beilstein J Org Chem. 2013;9:15-25. doi: 10.3762/bjoc.9.3. Epub 2013 Jan 4. Choy JW, Bryant C, Calvet CM, Doyle PS, Gunatilleke SS, Leung SS, Ang KK, Chen S, Gut J, Oses-Prieto JA, Johnston JB, Arkin MR, Burlingame AL, Taunton J, Jacobson MP, McKerrow JM, Podust LM, Renslo AR.

Optimization of anti-Trypanosoma cruzi oxadiazoles leads to identification of compounds with efficacy in infected mice. Bioorg Med Chem. 2012 Nov 1;20(21):6423-33. doi: 10.1016/j.bmc.2012.08.047. Epub 2012 Aug 31. dos Santos Filho JM, Moreira DR, de Simone CA, Ferreira RS, McKerrow JH, Meira CS, Guimarães ET, Soares MB.

Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51. PLoS Negl Trop Dis. 2012;6(7):e1736. doi: 10.1371/journal.pntd.0001736. Epub 2012 Jul 31. Gunatilleke SS, Calvet CM, Johnston JB, Chen CK, Erenburg G, Gut J, Engel JC, Ang KK, Mulvaney J, Chen S, Arkin MR, McKerrow JH, Podust LM.

Trypanosoma cruzi heparin-binding proteins mediate the adherence of epimastigotes to the midgut epithelial cells of Rhodnius prolixus. Parasitology. 2012 May;139(6):735-43. doi: 10.1017/S0031182011002344. Epub 2012 Feb 7. Oliveira FO Jr, Alves CR, Souza-Silva F, Calvet CM, Côrtes LM, Gonzalez MS, Toma L, Bouças RI, Nader HB, Pereira MC.

The Trypanosoma cruzi protease cruzain mediates immune evasion. PLoS Pathog. 2011 Sep;7(9):e1002139. doi: 10.1371/journal.ppat.1002139. Epub 2011 Sep 1. Doyle PS, Zhou YM, Hsieh I, Greenbaum DC, McKerrow JH, Engel JC.

Cruzain : the path from target validation to the clinic. Adv Exp Med Biol. 2011;712:100-15. doi: 10.1007/978-1-4419-8414-2_7. Review. Sajid M, Robertson SA, Brinen LS, McKerrow JH.

Cysteine peptidases of kinetoplastid parasites. Adv Exp Med Biol. 2011;712:84-99. doi: 10.1007/978-1-4419-8414-2_6. Review. Caffrey CR, Lima AP, Steverding D.

Mining a cathepsin inhibitor library for new antiparasitic drug leads. PLoS Negl Trop Dis. 2011 May 3;5(5):e1023. doi: 10.1371/journal.pntd.0001023. Ang KK, Ratnam J, Gut J, Legac J, Hansell E, Mackey ZB, Skrzypczynska KM, Debnath A, Engel JC, Rosenthal PJ, McKerrow JH, Arkin MR, Renslo AR.

Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents. Bioorg Med Chem. 2010 Nov 15;18(22):7826-35. doi: 10.1016/j.bmc.2010.09.056. Epub 2010 Sep 29. Hernandes MZ, Rabello MM, Leite AC, Cardoso MV, Moreira DR, Brondani DJ, Simone CA, Reis LC, Souza MA, Pereira VR, Ferreira RS, McKerrow JH.

In vitro and in vivo studies of the trypanocidal properties of WRR-483 against Trypanosoma cruzi. PLoS Negl Trop Dis. 2010 Sep 14;4(9). doi:pii: e825. 10.1371/journal.pntd.0000825. Chen YT, Brinen LS, Kerr ID, Hansell E, Doyle PS, McKerrow JH, Roush WR.

Image-based high-throughput drug screening targeting the intracellular stage of Trypanosoma cruzi, the agent of Chagas' disease. Antimicrob Agents Chemother. 2010 Aug;54(8):3326-34. doi: 10.1128/AAC.01777-09. Epub 2010 Jun 14. Engel JC, Ang KK, Chen S, Arkin MR, McKerrow JH, Doyle PS.

Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. J Med Chem. 2010 Jul 8;53(13):4891-905. doi: 10.1021/jm100488w. Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser MJ, McKerrow JH, Maloney DJ, Irwin JJ, Shoichet BK.

A nonazole CYP51 inhibitor cures Chagas' disease in a mouse model of acute infection. Antimicrob Agents Chemother. 2010 Jun;54(6):2480-8. doi: 10.1128/AAC.00281-10. Epub 2010 Apr 12. Doyle PS, Chen CK, Johnston JB, Hopkins SD, Leung SS, Jacobson MP, Engel JC, McKerrow JH, Podust LM.

Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole. PLoS Negl Trop Dis. 2010 Apr 6;4(4):e651. doi: 10.1371/journal.pntd.0000651. Chen CK, Leung SS, Guilbert C, Jacobson MP, McKerrow JH, Podust LM.

Delineation of diverse macrophage activation programs in response to intracellular parasites and cytokines. PLoS Negl Trop Dis. 2010 Mar 30;4(3):e648. doi: 10.1371/journal.pntd.0000648. Zhang S, Kim CC, Batra S, McKerrow JH, Loke P.

Nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors as promising new leads for Chagas disease chemotherapy. J Med Chem. 2010 Feb 25;53(4):1763-73. doi: 10.1021/jm901633v. Brak K, Kerr ID, Barrett KT, Fuchi N, Debnath M, Ang K, Engel JC, McKerrow JH, Doyle PS, Brinen LS, Ellman JA.

Identification and optimization of inhibitors of Trypanosomal cysteine proteases: cruzain, rhodesain, and TbCatB. J Med Chem. 2010 Jan 14;53(1):52-60. doi: 10.1021/jm901069a. Mott BT, Ferreira RS, Simeonov A, Jadhav A, Ang KK, Leister W, Shen M, Silveira JT, Doyle PS, Arkin MR, McKerrow JH, Inglese J, Austin CP, Thomas CJ, Shoichet BK, Maloney DJ.

Two approaches to discovering and developing new drugs for Chagas disease. Mem Inst Oswaldo Cruz. 2009 Jul;104 Suppl 1:263-9. McKerrow JH, Doyle PS, Engel JC, Podust LM, Robertson SA, Ferreira R, Saxton T, Arkin M, Kerr ID, Brinen LS, Craik CS.

Novel non-peptidic vinylsulfones targeting the S2 and S3 subsites of parasite cysteine proteases. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6218-21. doi: 10.1016/j.bmcl.2009.08.098. Epub 2009 Sep 3. Bryant C, Kerr ID, Debnath M, Ang KK, Ratnam J, Ferreira RS, Jaishankar P, Zhao D, Arkin MR, McKerrow JH, Brinen LS, Renslo AR.

Divergent modes of enzyme inhibition in a homologous structure-activity series. J Med Chem. 2009 Aug 27;52(16):5005-8. doi: 10.1021/jm9009229. Ferreira RS, Bryant C, Ang KK, McKerrow JH, Shoichet BK, Renslo AR.

Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J Biol Chem. 2009 Sep 18;284(38):25697-703. doi: 10.1074/jbc.M109.014340. Epub 2009 Jul 20. Kerr ID, Lee JH, Farady CJ, Marion R, Rickert M, Sajid M, Pandey KC, Caffrey CR, Legac J, Hansell E, McKerrow JH, Craik CS, Rosenthal PJ, Brinen LS.

Kinetoplastid papain-like cysteine peptidases. Mol Biochem Parasitol. 2009 Sep;167(1):12-9. doi: 10.1016/j.molbiopara.2009.04.009. Epub 2009 May 3. Review. Caffrey CR, Steverding D.

Trypanosoma cruzi CYP51 inhibitor derived from a Mycobacterium tuberculosis screen hit. PLoS Negl Trop Dis. 2009;3(2):e372. doi: 10.1371/journal.pntd.0000372. Epub 2009 Feb 3. Chen CK, Doyle PS, Yermalitskaya LV, Mackey ZB, Ang KK, McKerrow JH, Podust LM.

Metal compounds for the treatment of parasitic diseases. J Inorg Biochem. 2008 Oct;102(10):1839-45. doi: 10.1016/j.jinorgbio.2008.05.010. Epub 2008 Jun 4. Erratum in: J Inorg Biochem. 2009 May;103(5):869. Fricker SP, Mosi RM, Cameron BR, Baird I, Zhu Y, Anastassov V, Cox J, Doyle PS, Hansell E, Lau G, Langille J, Olsen M, Qin L, Skerlj R, Wong RS, Santucci Z, McKerrow JH.

Synthesis of macrocyclic trypanosomal cysteine protease inhibitors. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5860-3. doi: 10.1016/j.bmcl.2008.06.012. Epub 2008 Jun 10. Chen YT, Lira R, Hansell E, McKerrow JH, Roush WR.

Identification of a new class of nonpeptidic inhibitors of cruzain. J Am Chem Soc. 2008 May 21;130(20):6404-10. doi: 10.1021/ja710254m. Epub 2008 Apr 25. Brak K, Doyle PS, McKerrow JH, Ellman JA.

Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from trypanosomes. Bioorg Med Chem Lett. 2008 Jan 15;18(2):624-8. Epub 2007 Nov 22. Jaishankar P, Hansell E, Zhao DM, Doyle PS, McKerrow JH, Renslo AR.

Proteases in parasitic diseases. Annu Rev Pathol. 2006;1:497-536. Review. McKerrow JH, Caffrey C, Kelly B, Loke P, Sajid M.

Dipeptidyl-alpha,beta-epoxyesters as potent irreversible inhibitors of the cysteine proteases cruzain and rhodesain. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6697-700. Epub 2007 Oct 22. González FV, Izquierdo J, Rodríguez S, McKerrow JH, Hansell E.

A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection. Antimicrob Agents Chemother. 2007 Nov;51(11):3932-9. Epub 2007 Aug 13. Doyle PS, Zhou YM, Engel JC, McKerrow JH.

The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family. Structure. 2007 May;15(5):535-43. Wang SX, Pandey KC, Scharfstein J, Whisstock J, Huang RK, Jacobelli J, Fletterick RJ, Rosenthal PJ, Abrahamson M, Brinen LS, Rossi A, Sali A, McKerrow JH.

Cysteine proteinase inhibitors as therapy for parasitic diseases: advances in inhibitor design. Mini Rev Med Chem. 2006 Sep;6(9):1025-32. Review. Steverding D, Caffrey CR, Sajid M.

A cysteine protease inhibitor protects dogs from cardiac damage during infection by Trypanosoma cruzi. Antimicrob Agents Chemother. 2005 Dec;49(12):5160-1. Barr SC, Warner KL, Kornreic BG, Piscitelli J, Wolfe A, Benet L, McKerrow JH.

Genomic and proteomic approaches for Chagas' disease: critical analysis of diagnostic methods. Expert Rev Mol Diagn. 2005 Jul;5(4):521-30. Review. Huete-Pérez JA, Flores-Obando RE, Ghedin E, Caffrey CR.

Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain. Bioorg Med Chem Lett. 2005 Jan 3;15(1):121-3. Fujii N, Mallari JP, Hansell EJ, Mackey Z, Doyle P, Zhou YM, Gut J, Rosenthal PJ, McKerrow JH, Guy RK.

Peptidyl allyl sulfones: a new class of inhibitors for clan CA cysteine proteases. Bioorg Med Chem. 2004 Oct 1;12(19):5203-11. Götz MG, Caffrey CR, Hansell E, McKerrow JH, Powers JC.

Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain. Bioorg Med Chem Lett. 2003 Oct 20;13(20):3527-30. Chiyanzu I, Hansell E, Gut J, Rosenthal PJ, McKerrow JH, Chibale K.

Improved trypanocidal activities of cathepsin L inhibitors. Int J Antimicrob Agents. 2003 Aug;22(2):155-9. Nkemgu NJ, Grande R, Hansell E, McKerrow JH, Caffrey CR, Steverding D.

Synthesis and structure-activity relationship study of potent trypanocidal thio semicarbazone inhibitors of the trypanosomal cysteine protease cruzain. J Med Chem. 2002 Jun 20;45(13):2695-707. Du X, Guo C, Hansell E, Doyle PS, Caffrey CR, Holler TP, McKerrow JH, Cohen FE.

Cysteine proteases of parasitic organisms. Mol Biochem Parasitol. 2002 Mar;120(1):1-21. Review. Erratum in: Mol Biochem Parasitol 2002 Apr 30;121(1):159. Sajid M, McKerrow JH.

Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain. Bioorg Med Chem Lett. 2001 Oct 22;11(20):2759-62. Roush WR, Cheng J, Knapp-Reed B, Alvarez-Hernandez A, McKerrow JH, Hansell E, Engel JC.

Cysteine proteinases of trypanosome parasites: novel targets for chemotherapy. Curr Drug Targets. 2000 Sep;1(2):155-62. Review. Caffrey CR, Scory S, Steverding D.

A target within the target: probing cruzain's P1' site to define structural determinants for the Chagas' disease protease. Structure. 2000 Aug 15;8(8):831-40. Brinen LS, Hansell E, Cheng J, Roush WR, McKerrow JH, Fletterick RJ.

Aryl ureas represent a new class of anti-trypanosomal agents. Chem Biol. 2000 Sep;7(9):733-42. Du X, Hansell E, Engel JC, Caffrey CR, Cohen FE, McKerrow JH.

Upregulation of the secretory pathway in cysteine protease inhibitor-resistant Trypanosoma cruzi. J Cell Sci. 2000 Apr;113 ( Pt 8):1345-54. Erratum in: J Cell Sci 2000 Jul;113(Pt 14):2638. Garcia CT [corrected to Torres C]. Engel JC, Torres C, Hsieh I, Doyle PS, McKerrow JH.

The high stability of cruzipain against pH-induced inactivation is not dependent on its C-terminal domain. FEBS Lett. 2000 Mar 3;469(1):29-32. Stoka V, Turk B, McKerrow JH, Björk I, Cazzulo JJ, Turk V.

[Trypanocidal effect of cysteine protease inhibitors in vitro and in vivo in experimental Chagas disease]. Medicina (B Aires). 1999;59 Suppl 2:171-5. Review. Spanish. Engel JC, Doyle PS, McKerrow JH.

Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: insights on safety, target validation, and mechanism of action. Int J Parasitol. 1999 Jun;29(6):833-7. Review. McKerrow JH.

Cysteine protease inhibitors as chemotherapy for parasitic infections. Bioorg Med Chem. 1999 Apr;7(4):639-44. Review. McKerrow JH, Engel JC, Caffrey CR.

Protease trafficking in two primitive eukaryotes is mediated by a prodomain protein motif. J Biol Chem. 1999 Jun 4;274(23):16249-56. Huete-Pérez JA, Engel JC, Brinen LS, Mottram JC, McKerrow JH.

Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors. Bioorg Med Chem. 1998 Dec;6(12):2477-94. Scheidt KA, Roush WR, McKerrow JH, Selzer PM, Hansell E, Rosenthal PJ.

Design and synthesis of dipeptidyl alpha',beta'-epoxy ketones, potent irreversible inhibitors of the cysteine protease cruzain. Bioorg Med Chem Lett. 1998 Oct 6;8(19):2809-12. Roush WR, González FV, McKerrow JH, Hansell E.

Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med. 1998 Aug 17;188(4):725-34. Engel JC, Doyle PS, Hsieh I, McKerrow JH.

Substrate inhibition of cruzipain is not affected by the C-terminal domain. FEBS Lett. 1998 Jun 12;429(2):129-33. Stoka V, McKerrow JH, Cazzulo JJ, Turk V.

Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J Cell Sci. 1998 Mar;111 ( Pt 5):597-606. Engel JC, Doyle PS, Palmer J, Hsieh I, Bainton DF, McKerrow JH.

Structure-based design of parasitic protease inhibitors. Bioorg Med Chem. 1996 Sep;4(9):1421-7. Li R, Chen X, Gong B, Selzer PM, Li Z, Davidson E, Kurzban G, Miller RE, Nuzum EO, McKerrow JH, Fletterick RJ, Gillmor SA, Craik CS, Kuntz ID, Cohen FE, Kenyon GL.

The cysteine protease of Trypanosoma cruzi as a model for antiparasite drug design. Parasitol Today. 1995 Aug;11(8):279-82. McKerrow JH, McGrath ME, Engel JC.

The crystal structure of cruzain: a therapeutic target for Chagas' disease. J Mol Biol. 1995 Mar 24;247(2):251-9. McGrath ME, Eakin AE, Engel JC, McKerrow JH, Craik CS, Fletterick RJ.

Production of crystallizable cruzain, the major cysteine protease from Trypanosoma cruzi. J Biol Chem. 1993 Mar 25;268(9):6115-8. Eakin AE, McGrath ME, McKerrow JH, Fletterick RJ, Craik CS.

Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi. Mol Biochem Parasitol. 1993 Mar;58(1):17-24. Harth G, Andrews N, Mills AA, Engel JC, Smith R, McKerrow JH.

The sequence, organization, and expression of the major cysteine protease (cruzain) from Trypanosoma cruzi. J Biol Chem. 1992 Apr 15;267(11):7411-20. Eakin AE, Mills AA, Harth G, McKerrow JH, Craik CS.

New insights into the structure of a Trypanosoma cruzi protease. Parasitol Today. 1991 Jun;7(6):132-3. No abstract available. McKerrow JH.