Kinetoplastid papain-like cysteine peptidases

Molecular and Biochemical Parasitology

Volumn 167, Issue 1, 2009, Pages 12-19

  Caffrey, Conor R ^a   Steverding, Dietmar ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF EAST ANGLIA   (United Kingdom)

Author keywords

C1 cysteine peptidase; Cathepsin; Chemotherapy; Cryptobia; Diagnosis; Leishmania; Nomenclature; Parasite; Trypanosoma; Vaccine

Indexed keywords

ANTITRYPANOSOMAL AGENT; C1 PEPTIDASE INHIBITOR; CATHEPSIN B; CATHEPSIN L; K 11777; PAPAIN; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG; CYSTEINE PROTEINASE; DIAGNOSTIC AGENT; PARASITE ANTIGEN; PROTOZOAL VACCINE;

AMINO ACID SEQUENCE; CHAGAS DISEASE; DRUG EFFICACY; DRUG SYNTHESIS; DRUG TARGETING; FLAGELLATE INFECTION; FUNCTIONAL GENOMICS; GENE SILENCING; GENETIC CONSERVATION; HUMAN; LEISHMANIA; NONHUMAN; NUCLEOTIDE SEQUENCE; PARASITE SURVIVAL; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; PROTEIN TARGETING; REVIEW; RNA INTERFERENCE; TREATMENT DURATION; TRYPANOSOMA; TRYPANOSOMIASIS; ANIMAL; CHEMISTRY; CLASSIFICATION; ENZYMOLOGY; FLAGELLATE; GENETICS; IMMUNOLOGY; NOMENCLATURE; PHYSIOLOGY;

CRYPTOBIA; KINETOPLASTIDA; MAMMALIA; TRYPANOSOMA;

ANIMALS; ANTIGENS, PROTOZOAN; CYSTEINE ENDOPEPTIDASES; KINETOPLASTIDA; PROTOZOAN VACCINES; TERMINOLOGY AS TOPIC;

EID: 67650351943     PISSN: 01666851     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molbiopara.2009.04.009     Document Type: Review

References (108)

1. López-Otín C., and Bond J.S. Proteases: multifunctional enzymes in life and disease. J Biol Chem 283 (2008) 30433-30437
2. MEROPS, the Peptidase Database. 2008; http://merops.sanger.ac.uk/.
3. Mottram J.C., Brooks D.R., and Coombs G.H. Roles of cysteine proteinases of trypanosomes and Leishmania in host-parasite interactions. Curr Opin Microbiol 1 (1998) 455-460
4. Mottram J.C., Coombs G.H., and Alexander J. Cysteine peptidases as virulence factors of Leishmania. Curr Opin Microbiol 7 (2004) 375-381
5. Steverding D., Caffrey C.R., and Sajid M. Cysteine proteinase inhibitors as therapy for parasitic diseases: advances in inhibitor design. Mini Rev Med Chem 6 (2006) 1025-1032
6. Abdulla M.H., O'Brien T., Mackey Z.B., Sajid M., Grab D.J., and McKerrow J.H. RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model. PLoS Negl Trop Dis 2 (2008) e298
7. Engel J.C., Doyle P.S., Hsieh I., and McKerrow J.H. Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med 188 (1998) 725-734
8. Mottram J.C., Helms M.J., Coombs G.H., and Sajid M. Clan CD cysteine peptidases of parasitic protozoa. Trends Parasitol 19 (2003) 182-187
9. Sajid M., and McKerrow J.H. Cysteine proteases of parasitic organisms. Mol Biochem Parasitol 120 (2002) 1-21
10. Cazzulo J.J., Cazzulo Franke M.C., Martínez J., and Franke de Cazzulo B.M. Some kinetic properties of a cysteine proteinase (cruzipain) from Trypanosoma cruzi. Biochem Biophys Acta 1037 (1990) 186-191
11. Caffrey C.R., Scory S., and Steverding D. Cysteine proteinases of trypanosome parasites: novel targets for chemotherapy. Curr Drug Targets 1 (2000) 155-162
12. Eakin A.E., Mills A.A., Harth G., McKerrow J.H., and Craik C.S. The sequence, organization, and expression of the major cysteine protease (cruzain) from Trypanosoma cruzi. J Biol Chem 267 (1992) 7411-7420
13. Caffrey C.R., Hansell E., Lucas K.D., et al. Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense. Mol Biochem Parasitol 118 (2001) 61-73
14. Clayton C., Adams M., Almeida R., et al. Genetic nomenclature for Trypanosoma and Leishmania. Mol Biochem Parasitol 97 (1998) 221-224
15. Rawlings N.D., Morton F.R., Kok C.Y., Kong J., and Barrett A.J. MEROPS: the peptidase database. Nucleic Acids Res 36 (2008) D320-D325
16. Lecaille F., Kaleta J., and Brömme D. Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. Chem Rev 102 (2002) 4459-4488
17. Huete-Pérez J.A., Engel J.C., Brinen L.S., Mottram J.C., and McKerrow J.H. Protease trafficking in two primitive eukaryotes is mediated by a prodomain protein motif. J Biol Chem 274 (1999) 16249-16256
18. Ogino T., Kaji T., Kawabata M., et al. Function of the propeptide region in recombinant expression of active procathepsin L in Escherichia coli. J Biochem 126 (1999) 78-83
19. González G., Sunnemark D., Orn A., and Grönvik K.O. Detection of cruzipain, the major cysteine proteinase from Trypanosoma cruzi and its C-terminal extension in biological fluids during experimental infection in mice. Scand J Immunol 44 (1996) 122-128
20. Scharfstein J., Luquetti A., Murta A.C., et al. Chagas' disease: serodiagnosis with purified Gp25 antigen. Am J Trop Med Hyg 34 (1985) 1153-1160
21. Martínez J., Campetella O., Frasch A.C., and Cazzulo J.J. The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is antigenic in human infections. Infect Immun 59 (1991) 4275-4277
22. Martínez J., Campetella O., Frasch A.C., and Cazzulo J.J. The reactivity of sera from chagasic patients against different fragments of cruzipain, the major cysteine proteinase from Trypanosoma cruzi, suggests the presence of defined antigenic and catalytic domains. Immunol Lett 35 (1993) 191-196
23. Musil D., Zucic D., Turk D., et al. The refined 2.15 Å X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J 10 (1991) 2321-2330
24. Karrer K.M., Peiffer S.L., and DiThomas M.E. Two distinct gene subfamilies within the family of cysteine protease genes. Proc Natl Acad Sci USA 90 (1993) 3063-3067
25. Krupa J.C., Hasnain S., Nägler D.K., Ménard R., and Mort J.S. S2′ substrate specificity and the role of His110 and His111 in the exopeptidase activity of human cathepsin B. Biochem J 361 (2002) 613-619
26. Mottram J.C., North M.J., Barry D.J., and Coombs G.H. A cysteine proteinase cDNA from Trypanosoma brucei predicts an enzyme with an unusual C-terminal extension. FEBS Lett 258 (1989) 211-215
27. Cazzulo J.J., Stoka V., and Turk V. The major cysteine proteinase of Trypanosoma cruzi: a valid target for chemotherapy of Chagas disease. Curr Pharm Des 7 (2001) 1143-1156
28. Campetella O., Henriksson J., Aslund L., Frasch A.C., Pettersson U., and Cazzulo J.J. The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is encoded by multiple polymorphic tandemly organized genes located on different chromosomes. Mol Biochem Parasitol 50 (1992) 225-234
29. Lima A.P., Tessier D.C., Thomas D.Y., Scharfstein J., Storer A.C., and Vernet T. Identification of new cysteine protease gene isoforms in Trypanosoma cruzi. Mol Biochem Parasitol 67 (1994) 333-338
30. Mundodi V., Somanna A., Farrell P.J., and Gedamu L. Genomic organization and functional expression of differentially regulated cysteine protease genes of Leishmania donovani complex. Gene 282 (2002) 257-265
31. Sakanari J.A., Nadler S.A., Chan V.J., Engel J.C., Leptak C., and Bouvier J. Leishmania major: comparison of the cathepsin L- and B-like cysteine protease genes with those of other trypanosomatids. Exp Parasitol 85 (1997) 63-76
32. Mottram J.C., Souza A.E., Hutchison J.E., Carter R., Frame M.J., and Coombs G.H. Evidence from disruption of the lmcpb gene array of Leishmania mexicana that cysteine proteinases are virulence factors. Proc Natl Acad Sci USA 93 (1996) 6008-6013
33. Traub-Cseko Y.M., Duboise M., Boukai L.K., and McMahon-Pratt D. Identification of two distinct cysteine proteinase genes of Leishmania pifanoi axenic amastigotes using the polymerase chain reaction. Mol Biochem Parasitol 57 (1993) 101-105
34. Bart G., Coombs G.H., and Mottram J.C. Isolation of lmcpc, a gene encoding a Leishmania mexicana cathepsin-B-like cysteine proteinase. Mol Biochem Parasitol 73 (1995) 271-274
35. Somanna A., Mundodi V., and Gedamu L. Functional analysis of cathepsin B-like cysteine protease from Leishmania donovani complex. Evidence for activation of latent transforming growth factor β. J Biol Chem 277 (2002) 25305-25312
36. Nóbrega O.T., Santos Silva M.A., Teixeira A.R., and Santana J.M. Cloning and sequencing of tccb, a gene encoding a Trypanosoma cruzi cathepsin B-like protease. Mol Biochem Parasitol 97 (1998) 235-240
37. Mendoza-Palomares C., Biteau N., Giroud C., et al. Molecular and biochemical characterization of a cathepsin B-like protease family unique to Trypanosoma congolense. Eukaryot Cell 7 (2008) 684-697
38. Merckelbach A., Hasse S., Dell R., Eschlbeck A., and Ruppel A. cDNA sequences of Schistosoma japonicum coding for two cathepsin B-like proteins and Sj32. Trop Med Parasitol 45 (1994) 193-198
39. McCoubrie J.E., Miller S.K., Sargeant T., et al. Evidence for a common role for the serine-type Plasmodium falciparum serine repeat antigen proteases: implication for vaccine and drug design. Infect Immun 75 (2007) 5565-5574
40. Pamer E.G., So M., and Davis C.E. Identification of a developmentally regulated cysteine protease of Trypanosoma brucei. Mol Biochem Parasitol 33 (1989) 27-32
41. Mbawa Z.R., Gumm I.D., Shaw E., and Lonsdale-Eccles J.D. Characterisation of a cysteine protease from bloodstream forms of Trypanosoma congolense. Eur J Biochem 204 (1992) 371-379
42. 2. Exp Parasitol 91 (1999) 327-333
43. Mbawa Z.R., Webster P., and Lonsdale-Eccles J.D. Immunolocalization of a cysteine protease within the lysosomal system of Trypanosoma congolense. Eur J Cell Biol 56 (1991) 243-250
44. Tomás A.M., and Kelly J.M. Stage-regulated expression of cruzipain, the major cysteine protease of Trypanosoma cruzi is independent of the level of RNA1. Mol Biochem Parasitol 76 (1996) 91-103
45. Bontempi E., Martínez J., and Cazzulo J.J. Subcellular localization of a cysteine proteinase from Trypanosoma cruzi. Mol Biochem Parasitol 33 (1989) 43-47
46. Nascimento A.E., and de Souza W. High resolution localization of cruzipain and Ssp4 in Trypanosoma cruzi by replica staining label fracture. Biol Cell 86 (1996) 53-58
47. Engel J.C., Doyle P.S., Palmer J., Hsieh I., Bainton D.F., and McKerrow J.H. Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J Cell Sci 111 (1998) 597-606
48. Sant'Anna C., Parussini F., Lourenço D., de Souza W., Cazzulo J.J., and Cunha-e-Silva N.L. All Trypanosoma cruzi developmental forms present lysosome-related organelles. Histochem Cell Biol 130 (2008) 1187-1198
49. Pupkis M.F., Tetley L., and Coombs G.H. Leishmania mexicana: amastigote hydrolases in unusual lysosomes. Exp Parasitol 62 (1986) 29-39
50. Leon L.L., Temporal R.M., Soares M.J., and Grimaldi Júnior G. Proteinase activities during temperature-induced stage differentiation of species complexes of Leishmania. Acta Trop 56 (1994) 289-298
51. Duboise S.M., Vannier-Santos M.A., Costa-Pinto D., et al. The biosynthesis, processing, and immunolocalization of Leishmania pifanoi amastigote cysteine proteinases. Mol Biochem Parasitol 68 (1994) 119-132
52. Brooks D.R., Denise H., Westrop G.D., Coombs G.H., and Mottram J.C. The stage-regulated expression of Leishmania mexicana CPB cysteine proteases is mediated by an intercistronic sequence element. J Biol Chem 276 (2001) 47061-47069
53. Mackey Z.B., O'Brien T.C., Greenbaum D.C., Blank R.B., and McKerrow J.H. A cathepsin B-like protease is required for host protein degradation in Trypanosoma brucei. J Biol Chem 279 (2004) 48426-48433
54. Garcia M.P., Nóbrega O.T., Teixeira A.R.L., Sousa M.V., and Santana J.M. Characterisation of a Trypanosoma cruzi acidic 30 kDa cysteine protease. Mol Biochem Parasitol 91 (1998) 263-272
55. McKerrow J.H., Caffrey C., Kelly B., Loke P., and Sajid M. Proteases in parasitic diseases. Annu Rev Pathol 1 (2006) 497-536
56. O'Brien T.C., Mackey Z.B., Fetter R.D., et al. A parasite cysteine protease is key to host protein degradation and iron acquisition. J Biol Chem 283 (2008) 28934-28943
57. Dautry-Varsat A., Ciechanover A., and Lodish H.F. pH and the recycling of transferrin during receptor-mediated endocytosis. Proc Natl Acad Sci USA 80 (1983) 2258-2262
58. Maier A., and Steverding D. Low affinity of Trypanosoma brucei transferrin receptor to apotransferrin at pH 5 explains the fate of the ligand during endocytosis. FEBS Lett 396 (1996) 87-89
59. Grab D.J., Wells C.W., Shaw M.K., Webster P., and Russo D.C. Endocytosed transferrin in African trypanosomes is delivered to lysosomes and may not be recycled. Eur J Cell Biol 59 (1992) 398-404
60. Steverding D., Stierhof Y.D., Fuchs H., Tauber R., and Overath P. Transferrin-binding protein complex is the receptor for transferrin uptake in Trypanosoma brucei. J Cell Biol 131 (1995) 1173-1182
61. Kabiri M., and Steverding D. Studies on the recycling of the transferrin receptor in Trypanosoma brucei using an inducible gene expression system. Eur J Biochem 267 (2000) 3309-3314
62. Steverding D. The transferrin receptor of Trypanosoma brucei. Parasitol Int 48 (2000) 191-198
63. Steverding D. Parasites' receptors for human transferrin and lactoferrin. In: Fuchs H. (Ed). Iron metabolism and disease (2008), Research Signpost, Kerala 421-434
64. Nikolskaia O.V., de A Lima A.P., Kim Y.V., et al. Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease. J Clin Invest 116 (2006) 2739-2747
65. Ashall F., Angliker H., and Shaw E. Lysis of trypanosomes by peptidyl fluoromethyl ketones. Biochem Biophys Res Commun 170 (1990) 923-929
66. Meirelles M.N., Juliano L., Carmona E., et al. Inhibitors of the major cysteinyl proteinase (GP57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vitro. Mol Biochem Parasitol 52 (1992) 175-184
67. Harth G., Andrews N., Mills A.A., Engel J.C., Smith R., and McKerrow J.H. Peptide-fluoromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi. Mol Biochem Parasitol 58 (1993) 17-24
68. Franke de Cazzulo B.M., Martínez J., North M.J., Coombs G.H., and Cazzulo J.J. Effects of proteinase inhibitors on the growth and differentiation of Trypanosoma cruzi. FEMS Microbiol Lett 124 (1994) 81-86
69. Aparicio I.M., Scharfstein J., and Lima A.P. A new cruzipain-mediated pathway of human cell invasion by Trypanosoma cruzi requires trypomastigote membranes. Infect Immun 72 (2004) 5892-5902
70. Del Nery E., Juliano M.A., Lima A.P., Scharfstein J., and Juliano L. Kininogenase activity by the major cysteinyl proteinase (cruzipain) from Trypanosoma cruzi. J Biol Chem 272 (1997) 25713-25718
71. Scharfstein J., Schmitz V., Morandi V., et al. Host cell invasion by Trypanosoma cruzi is potentiated by activation of bradykinin B(2) receptors. J Exp Med 192 (2000) 1289-1300
72. Denise H., McNeil K., Brooks D.R., Alexander J., Coombs G.H., and Mottram J.C. Expression of multiple CPB genes encoding cysteine proteases is required for Leishmania mexicana virulence in vivo. Infect Immun 71 (2003) 3190-3195
73. Frame M.J., Mottram J.C., and Coombs G.H. Analysis of the roles of cysteine proteinases of Leishmania mexicana in the host-parasite interaction. Parasitology 121 (2000) 367-377
74. Mahmoudzadeh-Niknam H., and McKerrow J.H. Leishmania tropica: cysteine proteases are essential for growth and pathogenicity. Exp Parasitol 106 (2004) 158-163
75. Mundodi V., Kucknoor A.S., and Gedamu L. Role of Leishmania (Leishmania) chagasi amastigote cysteine protease in intracellular parasite survival: studies by gene disruption and antisense mRNA inhibition. BMC Mol Biol 6 (2005) 3
76. Marín-Villa M., Vargas-Inchaustegui D.A., Chaves S.P., et al. The C-terminal extension of Leishmania pifanoi amastigote-specific cysteine proteinase Lpcys2: a putative function in macrophage infection. Mol Biochem Parasitol 162 (2008) 52-59
77. Alexander J., Coombs G.H., and Mootram J.C. Leishmania mexicana cysteine proteinase-deficient mutants have attenuated virulence for mice and potentiate a Th1 response. J Immunol 161 (1998) 6794-6801
78. Buxbaum L.U., Denise H., Coombs G.H., Alexander J., Mottram J.C., and Scott P. Cysteine protease B of Leishmania mexicana inhibits host Th1 response and protective immunity. J Immunol 171 (2003) 3711-3717
79. Cameron P., McGachy A., Anderson M., et al. Inhibition of lipopolysaccharide-induced macrophage IL-12 production by Leishmania mexicana amastigotes: the role of cysteine peptidases and the NF-κB signaling pathway. J Immunol 173 (2004) 3297-3304
80. Svensjö E., Batista P.R., Brodskyn C.I., et al. Interplay between parasite cysteine proteases and the host kinin system modulates microvascular leakage and macrophage infection by promastigotes of Leishmania donovani complex. Microbes Infect 8 (2006) 206-220
81. Bart G., Frame M.J., Carter R., Coombs G.H., and Mottram J.C. Cathepsin B-like cysteine proteinase-deficient mutants of Leishmania mexicana. Mol Biochem Parasitol 88 (1997) 53-61
82. Gantt K.R., Schultz-Cherry S., Rodriguez N., et al. Activation of TGF-β by Leishmania chagasi: importance for parasite survival in macrophages. J Immunol 170 (2003) 2613-2620
83. Authié E., Duvallet G., Robertson C., and Williams D.J. Antibody responses to a 33 kDa cysteine protease of Trypanosoma congolense: relationship to 'trypanotolerance' in cattle. Parasite Immunol 15 (1993) 465-474
84. Authié E. Trypanosomiasis and trypanotolerance in cattle: a role for congopain?. Parasitol Today 10 (1994) 360-364
85. Authié E., Boulangé A., Muteti D., Lalmanch G., Gauthier F., and Musoke A.J. Immunisation of cattle with cysteine proteinases of Trypanosoma congolense: targetting the disease rather than the parasite. Int J Parasitol 31 (2001) 1429-1433
86. Schnapp A.R., Eickhoff C.S., Scharfstein J., and Hoft D.F. Induction of B- and T-cell responses to cruzipain in the murine model of Trypanosoma cruzi infection. Microbes Infect 4 (2002) 805-813
87. Cazorla S.I., Frank F.M., Becker P.D., Corral R.S., Guzmán C.A., and Malchiodi E.L. Prime-boost immunization with cruzipain co-administered with MALP-2 triggers a protective immune response able to decrease parasite burden and tissue injury in an experimental Trypanosoma cruzi infection model. Vaccine 26 (2008) 1999-2009
88. Cazorla S.I., Becker P.D., Frank F.M., et al. Oral vaccination with Salmonella enterica as a cruzipain-DNA delivery system confers protective immunity against Trypanosoma cruzi. Infect Immun 76 (2008) 324-333
89. Rafati S., Salmanian A.H., Taheri T., Vafa M., and Fasel N. A protective cocktail vaccine against murine cutaneous leishmaniasis with DNA encoding cysteine proteinases of Leishmania major. Vaccine 19 (2001) 3369-3375
90. Rafati S., Zahedifard F., and Nazgouee F. Prime-boost vaccination using cysteine proteinases type I and II of Leishmania infantum confers protective immunity in murine visceral leishmaniasis. Vaccine 24 (2006) 2169-2175
91. Ferreira J.H., Gentil L.G., Dias S.S., Fedeli C.E., Katz S., and Barbiéri C.L. Immunization with the cycteine proteinase Ldccys1 gene from Leishmania (Leishmania) chagasi and the recombinant Ldccys1 protein elicits protective immune responses in a murine model of visceral leishmaniasis. Vaccine 26 (2008) 677-685
92. Pollock K.G., McNeil K.S., Mottram J.C., et al. The Leishmania mexicana cysteine protease, CPB2.8, induces potent Th2 responses. J Immunol 170 (2003) 1746-1753
93. Khoshgoo N., Zahedifard F., Azizi H., Taslimi Y., Alonso M.J., and Rafati S. Cysteine proteinase type III is protective against Leishmania infantum infection in BALB/c mice and highly antigenic in visceral leishmaniasis individuals. Vaccine 26 (2008) 5822-5829
94. Authié E., Muteti D.K., and Williams D.J. Antibody responses to invariant antigens of Trypanosoma congolense in cattle of differing susceptibility to trypanosomiasis. Parasite Immunol 15 (1993) 101-111
95. Scharfstein J., Rodrigues M.M., Alves C.A., de Souza W., Previato J.O., and Mendonça-Previato L. Trypanosoma cruzi: description of a highly purified surface antigen defined by human antibodies. J Immunol 131 (1983) 972-976
96. Caffrey C.R., and Steverding D. Recent initiatives and strategies to developing new drugs for tropical parasitic diseases. Expert Opin Drug Discov 3 (2008) 173-186
97. Engel J.C., Doyle P.S., and McKerrow J.H. Efecto antiparasitario de inhibidores de cisteín proteasas in vitro e in vivo en la enfermedad de Chagas experimental. Medicina (B Aires) 59 Suppl. 2 (1999) 171-175
98. Abdulla M.H., Lim K.C., Sajid M., McKerrow J.H., and Caffrey C.R. Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor. PLoS Med 4 (2007) e14
99. Troeberg L., Morty R.E., Pike R.N., et al. Cysteine proteinase inhibitors kill cultured bloodstream forms of Trypanosoma brucei brucei. Exp Parasitol 91 (1999) 349-355
100. Nkemngu N.J., Grande R., Hansell E., McKerrow J.H., Caffrey C.R., and Steverding D. Improved trypanocidal activities of cathepsin L inhibitors. Int J Antimicrob Agents 22 (2003) 155-159
101. Vicik R., Hoerr V., Glaser M., et al. Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents. Bioorg Med Chem Lett 16 (2006) 2753-2757
102. Chen Y.T., Lira R., Hansell E., McKerrow J.H., and Roush W.R. Synthesis of macrocyclic trypanosomal cysteine protease inhibitors. Bioorg Med Chem Lett 18 (2008) 5860-5863
103. Mallari J.P., Shelat A., Kosinski A., et al. Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg Med Chem Lett 18 (2008) 2883-2885
104. Turk B. Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discov 5 (2006) 785-799
105. Renslo A.R., and McKerrow J.H. Drug discovery and development for neglected parasitic diseases. Nat Chem Biol 2 (2006) 701-710
106. 2 alters cell morphology and cell division activity of Trypanosoma brucei bloodstreams forms in vivo. Kinetoplastid Biol Dis 6 (2007) 2
107. Selzer P.M., Pingel S., Hsieh I., et al. Cysteine protease inhibitors as chemotherapy: lessons from a parasite target. Proc Natl Acad Sci USA 96 (1999) 11015-11022
108. Steert K., El-Sayed I., Van der Veken P., et al. Dipeptidyl α-fluorovinyl Michael acceptors: synthesis and activity against cysteine proteases. Bioorg Med Chem Lett 17 (2007) 6563-6566