Fairlamb, Alan - Division of Biological Chemistry and Molecular Microbiology, University of Dundee

• Molecular & Biochemical Parasitology 115 (2001) 189198 Ovothiol and trypanothione as antioxidants in trypanosomatids
• Glutathione-like Tripeptides as Inhibitors of Glutathionylspermidine Synthetase. Part 2: Substitution of the
• Edited by A.H. Fairlamb, R.G. Ridley, H.J. Vial Drugs against parasitic diseases
• ISOLATION AND CHARACTERIZATION OF KINETOPLAST DNA FROM BLOODSTREAM FORM OF TRYPANOSOMA BRUCEI
• Proc. Nati. Acad. Sci. USA Vol. 85, pp. 5374-5378, August 1988
• Reprinted from J. llol. Biol. (1592\227.322-333 Active Site of Trypanothione Reductase
• Protein Science (1992),f, 874-883. Cambridge University Press. Printed in the USA. Copyright 0 1992The Protein Society
• Eur. J. Biochem. 218, 29-37 (1993) Phenotype of recombinant Leishmania donovani and Trypanosoma cruzi
• Acta Cryst. (1994). B50, 139-154 Structure of Trypanothione Reductase from Crithidia fasciculata at 2.6 ,~
• Eur. J. Biochem. 226, 1019-1027 (1994) Identification and biosynthesis
• Eur. J. Biochem. 230,460-468 (1995) Trypanothione reductase from Leishmania donovani
• Glutathionyispermidine metabolism in Escherichia coli Keith SMITH, Adolfo BORGES,t Mark R. ARIYANAYAGAM and Alan H. FAIRLAMB*
• ProteinScience (1996), 5:52-61. Cambridge University Press. Printed in the USA. Copyright 0 1996 The Protein Society
• Pergamon Bioorganic & Medicinal Chemistry, Vol. 5, No. 12, pp 2185-2192, 1997 ~i~ 1997 Elsevier Science Ltd
• The EMBO Journal Vol.16 No.10 pp.25902598, 1997 Disruption of the trypanothione reductase gene of
• Biochem. J. (1998) 334, 437445 (Printed in Great Britain) 437 Detailed characterization of a cyclophilin from the human malaria parasite
• Molecular and Biochemical Parasitology 96 (1998) 111123 Cloning, expression and reconstitution of the
• 7 R1 = OMe, R2 = H 8 n = 1, R1
• Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery
• Ornithine Decarboxylase Gene Deletion Mutants of Leishmania donovani*
• CRYSTALLIZATION NOTE Crystallization of Recombinant Crithidia fasciculata Tryparedoxin
• Molecular and Biochemical Parasitology 99 (1999) 167181 Characterization of protein Ser/Thr phosphatases of the malaria
• Molecular and Biochemical Parasitology 103 (1999) 6169 Entamoeba histolytica lacks trypanothione metabolism
• Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to
• The Three-dimensional Structure of a Plasmodium falciparum Cyclophilin in Complex with the Potent
• Synthesis and Evaluation of 9,9-Dimethylxanthene Tricyclics Against Trypanothione Reductase, Trypanosoma brucei,
• The Structure of Reduced Tryparedoxin Peroxidase Reveals a Decamer and Insight into Reactivity of
• Molecular and Biochemical Parasitology 111 (2000) 4149 Cloning, expression and functional characterisation of a
• Antiprotozoal and Cytotoxicity Evaluation of Sulfonamide and Urea Analogues of Quinacrine
• A new expression vector for Crithidia fasciculata and Leishmania Emmanuel Tetaud a,b,*, Isabelle Lecuix b
• Amino Acids (2002) 22: 297308 Peptoid inhibition of trypanothione reductase as a potential
• Properties of Phosphoenolpyruvate Mutase, the First Enzyme in the Aminoethylphosphonate Biosynthetic Pathway in
• Benzofuranyl 3,5-bis-Polyamine Derivatives as Time-Dependent Inhibitors of Trypanothione Reductase
• Trypanothione S-Transferase Activity in a Trypanosomatid Ribosomal Elongation Factor 1B*
• crystallization communications Acta Cryst. (2005). F61, 769772 doi:10.1107/S174430910502169X 769
• EUKARYOTIC CELL, Dec. 2005, p. 20572065 Vol. 4, No. 12 1535-9778/05/$08.00 0 doi:10.1128/EC.4.12.20572065.2005
• Differential toxicity of antimonial compounds and their effects on glutathione homeostasis in a human leukaemia
• Molecular Microbiology (2006) 59(4), 12391248 doi:10.1111/j.1365-2958.2005.05022.x First published online 9 January 2006
• Acta Tropica 97 (2006) 364369 Refinement of techniques for the propagation of Leishmania
• Molecular & Biochemical Parasitology 149 (2006) 117120 Short communication
• Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening
• A comparative study of type I and type II tryparedoxin peroxidases in Leishmania major
• ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 2008, p. 13591365 Vol. 52, No. 4 0066-4804/08/$08.00 0 doi:10.1128/AAC.01563-07
• Leishmania Trypanothione Synthetase-Amidase Structure Reveals a Basis for Regulation of Conflicting Synthetic and
• Chemical and genetic validation of dihydrofolate reductasethymidylate synthase as a drug target in
• ATP-dependent ligases in trypanothione biosynthesis kinetics of catalysis and inhibition
• DOI: 10.1002/cmdc.200900098 Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-
• Chemical Validation of Trypanothione Synthetase A POTENTIAL DRUG TARGET FOR HUMAN TRYPANOSOMIASIS*S
• DOI: 10.1002/cmdc.200900262 Investigation of Trypanothione Reductase as a Drug Target
• N-myristoyltransferase inhibitors as new leads to treat sleeping sickness
• Annu. Rev. Microbiol. 1998. 52:74578 Copyright c 1998 by Annual Reviews. All rights reserved
• FUTURE PROSPECTS FOR CHAGAS' DISEASE CHEMOTHERAPY 179 MEDICINA (Buenos Aires) 1999; 59 (Supl. II): 179-187PROBLEMATICA DE LA ENFERMEDAD DE CHAGAS
• Drugs against parasitic diseases: R&D methodologies and issues SECTION III A. H. FAIRLAMB 107 Target discovery and validation with
• CLINICAL MICROBIOLOGY REVIEWS, Jan. 2006, p. 111126 Vol. 19, No. 1 0893-8512/06/$08.00 0 doi:10.1128/CMR.19.1.111126.2006
• This article was published in an Elsevier journal. The attached copy is furnished to the author for non-commercial research and
• Biochem. J. (2006) 393, 447457 (Printed in Great Britain) doi:10.1042/BJ20050832 447 Kinetic, inhibition and structural studies on 3-oxoacyl-ACP reductase from
• Molecular & Biochemical Parasitology 173 (2010) 162164 Contents lists available at ScienceDirect
• Chemotherapy of human African trypanosomiasis: current and future
• Biochem. J. (1996) 316, 481486 (Printed in Great Britain) 481 Regulation of a high-affinity diamine transport system in Trypanosoma cruzi
• Biochemistry 1986, 25, 3519-3526 3519 Purification and Characterization of Trypanothione Reductase from Crithidia
• ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, July 2009, p. 28242833 Vol. 53, No. 7 0066-4804/09/$08.00 0 doi:10.1128/AAC.01568-08
• DESIGN OF ANTIPARASITIC DRUGS Acta Cryst. (1995). D51, 567-574-
• Biochem. J. (2006) 400, 217223 (Printed in Great Britain) doi:10.1042/BJ20060882 217 Trypanothione-dependent glyoxalase I in Trypanosoma cruzi
• ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, July 2010, p. 28932900 Vol. 54, No. 7 0066-4804/10/$12.00 doi:10.1128/AAC.00332-10
• Phenothiazine Inhibitors of Trypanothione Reductase as Potential Antitrypanosomal and Antileishmanial Drugs
• 120 Report of the Scientific Working Group on Leishmaniasis, 2004 TDR/SWG/04 7.2 FROM GENOME TO
• Biochem. J. (1997) 325, 645651 (Printed in Great Britain) 645 Molecular characterization and expression of Onchocerca volvulus
• High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity
• Tryparedoxins from Crithidia fasciculata and Trypanosoma brucei PHOTOREDUCTION OF THE REDOX DISULFIDE USING SYNCHROTRON RADIATION AND EVIDENCE FOR A
• CHEMOTHERAPY F O R T R Y P A N O S O M I A S I S
• Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal
• Regiocontrolled synthesis of the macrocyclic polyamine alkaloid ()-lunarine, a time-dependent inhibitor of trypanothione reductase
• Full text access provided via ACS AuthorChoice Journal of Medicinal Chemistry is published by the American Chemical Society.
• pubs.acs.org/jmc Published on Web 06/15/2009 r 2009 American Chemical Society 4454 J. Med. Chem. 2009, 52, 44544465
• Review series TheJournalofClinicalInvestigation http://www.jci.org Volume118 Number4 April2008 1301
• Very Short and Efficient Syntheses of the Spermine Alkaloid Kukoamine A and Analogs Using Isolable Succinimidyl Cinnamates
• Exploring the potential of xanthene derivatives as trypanothione reductase inhibitors and chloroquine potentiating agents
• Published online 4 January 2002 Metabolic pathway analysis in trypanosomes
• Glutathione-like Tripeptides as Inhibitors of Glutathionylspermidine Synthetase. Part 1: Substitution of the
• Enzymatic Inhibitory Activity and Trypanocidal Effects of Extracts and Compounds from Siphoneugena densiflora O. Berg
• Molecular & Biochemical Parasitology 139 (2005) 107116 Trypanothione biosynthesis in Leishmania major
• The EMBO Journal vol.13 no.4 pp.898-905, 1994 A 7.1 kb linear DNA molecule of Theileria parva has
• WILLIAM CLEGG et al. 1953 CI1 -0.2214 (10) 1.0318 (7) -0.2976 (5) 0.0341 (13)
• 1996 Oxford University Press29422949 Nucleic Acids Research, 1996, Vol. 24, No. 15 Extrachromosomal, homologous expression of
• Biochem. J. (2002) 364, 679686 (Printed in Great Britain) 679 Characterization of recombinant glutathionylspermidine synthetase/amidase
• Computer assisted design of potentially active anti-trypanosomal Margot Paulinoa
• ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, June 1994, p. 1298-1302 0066-4804/94/$04.00+0
• Eur. J. Biochem. 213, 67-75 (1993) Substrate interactions between trypanothione reductase
• Biochem. J. (2003) 369, 529537 (Printed in Great Britain) 529 Ellman's-reagent-mediated regeneration of trypanothione in situ: substrate-
• Molecular & Biochemical Parasitology 131 (2003) 2533 Properties of trypanothione synthetase from Trypanosoma brucei
• Uptake of the Nitroimidazole Drug Megazol by African Trypanosomes
• Eur. J. Biochem. 228, 745-752 (1995) Site-directedmutagenesis of the redox-active cysteines
• Biochem. J. (2008) 414, 375381 (Printed in Great Britain) doi:10.1042/BJ20080889 375 Structural and mechanistic insights into type II trypanosomatid
• AnrinoAcids(1999)17:175-183 @ Springer-Verlag199)
• A comparative study of methylglyoxal metabolism in trypanosomatids
• Time-dependent inhibitors of trypanothione reductase: Analogues of the spermidine alkaloid lunarine and related natural products
• DOI: 10.1002/cmdc.200900097 Improved Tricyclic Inhibitors of Trypanothione Reductase
• A Single Enzyme Catalyses Formation of Trypanothione from Glutathione and Spermidine in Trypanosoma cruzi*
• Molecular & Biochemical Parasitology 169 (2010) 1219 Contents lists available at ScienceDirect
• R E S E A R C H A R T I C L E The Genome of the African Trypanosome
• Biochem. J. (2005) 391, 425432 (Printed in Great Britain) doi:10.1042/BJ20050911 425 Phenotypic analysis of trypanothione synthetase knockdown in the
• Dissecting the essentiality of the bifunctional trypanothione synthetase-amidase in Trypanosoma brucei using chemical
• Dual Action of Antimonial Drugs on Thiol Redox Metabolism in the Human Pathogen Leishmania donovani*
• Issue in Honor of Prof. Torbjorn Norin ARKIVOC 2008 (vi) 52-60 Inhibition of trypanothione reductase and glutathione reductase by
• Two Interacting Binding Sites for Quinacrine Derivatives in the Active Site of Trypanothione Reductase
• 1Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 98: 000-000, 2003 8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a
• ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, June 2007, p. 21642172 Vol. 51, No. 6 0066-4804/07/$08.00 0 doi:10.1128/AAC.01418-06
• Proc. Natl. Acad. Sci. USA Vol. 95, pp. 53115316, April 1998
• Resistance to currently used drugs is a serious problem in most fields of antimicrobial chemotherapy. Crossresistance
• Bis(glutathionyl)spermine and Other Novel Trypanothione Analogues in Trypanosoma cruzi*
• 4rrrrr /lLr. llrr,ilti,ti l9r: 1(; hl3--:v Coptlitht i l99l ht,4nnutl k r?.trr//r( ..1,'irir.'/rts,1.rrri(rr
• Increased levels of thiols protect antimony unresponsive Leishmania donovani field isolates against reactive oxygen
• Uptake of Diamidine Drugs by the P2 Nucleoside Transporter in Melarsen-sensitive and -resistant Trypanosoma brucei brucei*
• Cloning and Characterization of the Two Enzymes Responsible for Trypanothione Biosynthesis in Crithidia fasciculata*
• Molecular and Biochemical Parasitology 96 (1998) 125137 Identification and characterisation of a functional peroxidoxin
• The High Resolution Crystal Structure of Recombinant Crithidia fasciculata Tryparedoxin-I*
• Biochem. J. (1992) 286, 9-11 (Printed in Great Britain) RESEARCH COMMUNICATION
• Eur. J. Biocliem. 221, 285-295 (1994) Mechanism of inhibition of trypanothione reductase
• Molecular & Biochemical Parasitology 112 (2001) 183191 Cloning of a pyruvate phosphate dikinase from Trypanosoma
• Development and validation of a cytochrome c-coupled assay for pteridine reductase 1 and dihydrofolate reductase
• Proc. Natl. Acad. Sci. USA Vol. 86, pp. 2607-2611, April 1989
• Journal of General Microbiology ( I 988), 134, 807-8 17. Printed in Great Britain 807 Levels of Polyamines, Glutathione and Glutathione-Spermidine Conjugates
• Trypanothione: A Novel Bis(glutathionyl)spermidine Cofactor for Glutathione Reductase in Trypanosomatids
• Trypanosoma brucei pteridine reductase 1 is essential for survival in vitro and for virulence in micemmi_7236 658..671
• Molecular & Biochemical Parasitology 116 (2001) 171183 Molecular characterisation of mitochondrial and cytosolic
• DOI: 10.1002/cmdc.201100420 Design, Synthesis and Biological Evaluation of
• Quinol derivatives as potential trypanocidal agents Amy Capes a,
• DOI: 10.1002/cmdc.201100278 Optimisation of the Anti-Trypanosoma brucei Activity of
• Antitumor Quinol PMX464 Is a Cytocidal Anti-trypanosomal Inhibitor Targeting Trypanothione Metabolism*
• orbit their host star at distances closer than Mercury's orbit around the Sun (Fig. 1) --is
• Visceral Leishmaniasis and Arsenic: An Ancient Poison Contributing to Antimonial Treatment Failure in the
• Published: August 18, 2011 r 2011 American Chemical Society 6514 dx.doi.org/10.1021/jm200312v |J. Med. Chem. 2011, 54, 65146530
• DOI: 10.1002/cmdc.201000442 Synthesis and Evaluation of Indatraline-Based Inhibitors
• Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors
• Dissecting the Metabolic Roles of Pteridine Reductase 1 in Trypanosoma brucei and Leishmania major*
• Seminars in Cell & Developmental Biology 22 (2011) 271277 Contents lists available at ScienceDirect
• Current Topics in Medicinal Chemistry, 2011, 11, 1275-1283 1275 1568-0266/11 $58.00+.00 2011 Bentham Science Publishers Ltd.
• co r r e s p on d e n c e nature medicine volume 17 | number 1 | january 2011 33
• DOI: 10.1002/cmdc.201000450 Design, Synthesis and Biological Evaluation of Novel