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Professor Alan Fairlamb

TitleProfessor of Biochemistry
InstitutionUniversity of Dundee
DepartmentBiological Chemistry & Drug Discovery
AddressDundee
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    Collapse Overview 
    Collapse overview
    My research career has been devoted to the discovery and development of improved therapies for ‘neglected’ tropical diseases. The overarching theme of my research has been the discovery and detailed molecular characterisation of potential drug targets; and their assessment for essentiality and “druggability” by genetic and chemical methods.

    To bridge the translational gap from basic research to preclinical drug candidate, together with Professor Mike Ferguson, we founded the Drug Discovery Unit at the University of Dundee in 1995. In ten years of operation, it has grown from about 20 to over 80 scientific staff and has broadened its remit to include diseases of the developed world with unmet medical need. Currently, I am an advisor on several drug discovery projects for malaria, human African trypanosomiasis, Chagas’ disease and visceral leishmaniasis.

    My studies on the modes of action of existing drugs, and the mechanisms by which parasites develop resistance to them, has allowed me to explore broad areas of parasite metabolism, drug and nutrient transport and cell biology that differ significantly from their human hosts.

    My investigations into parasite antioxidant defences and the mode of action of arsenical drugs resulted in the discovery of trypanothione, a truly unique metabolite in trypanosomes and leishmania (kinetoplastids). My current basic research activities involve identification and molecular characterisation of novel drug targets and their validation using genetic and chemical approaches, with particular reference to trypanothione, polyamine, folic acid and biopterin metabolism. I am also working to identify the targets and mode of action of potent, novel cytocidal compounds identified from biological (phenotypic) screens.


    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Baragaña B, Hallyburton I, Lee MC, Norcross NR, Grimaldi R, Otto TD, Proto WR, Blagborough AM, Meister S, Wirjanata G, Ruecker A, Upton LM, Abraham TS, Almeida MJ, Pradhan A, Porzelle A, Martínez MS, Bolscher JM, Woodland A, Luksch T, Norval S, Zuccotto F, Thomas J, Simeons F, Stojanovski L, Osuna-Cabello M, Brock PM, Churcher TS, Sala KA, Zakutansky SE, Jiménez-Díaz MB, Sanz LM, Riley J, Basak R, Campbell M, Avery VM, Sauerwein RW, Dechering KJ, Noviyanti R, Campo B, Frearson JA, Angulo-Barturen I, Ferrer-Bazaga S, Gamo FJ, Wyatt PG, Leroy D, Siegl P, Delves MJ, Kyle DE, Wittlin S, Marfurt J, Price RN, Sinden RE, Winzeler EA, Charman SA, Bebrevska L, Gray DW, Campbell S, Fairlamb AH, Willis PA, Rayner JC, Fidock DA, Read KD, Gilbert IH. Corrigendum: A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature. 2016 09 01; 537(7618):122. PMID: 27281209.
      View in: PubMed
    2. Bruhn DF, Wyllie S, Rodríguez-Cortés A, Carrillo AK. Pentacyclic nitrofurans that rapidly kill nifurtimox-resistant trypanosomes. J Antimicrob Chemother. 2016 Apr; 71(4):956-63. PMID: 26682963; PMCID: PMC4790617 [Available on 04/01/17].
    3. Jones DC, Foth BJ, Urbaniak MD, Patterson S, Ong HB, Berriman M, Fairlamb AH. Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome. PLoS Negl Trop Dis. 2015 Dec; 9(12):e0004299. PMID: 26684831; PMCID: PMC4689576.
    4. Wyllie S, Foth BJ, Kelner A, Sokolova AY, Berriman M, Fairlamb AH. Nitroheterocyclic drug resistance mechanisms in Trypanosoma brucei. J Antimicrob Chemother. 2016 Mar; 71(3):625-34. PMID: 26581221; PMCID: PMC4743696.
    5. Baragaña B, Hallyburton I, Lee MC, Norcross NR, Grimaldi R, Otto TD, Proto WR, Blagborough AM, Meister S, Wirjanata G, Ruecker A, Upton LM, Abraham TS, Almeida MJ, Pradhan A, Porzelle A. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature. 2015 06 18; 522(7556):315-20. PMID: 26085270; PMCID: PMC4700930.
    6. Perry MR, Prajapati VK, Menten J, Raab A, Feldmann J, Chakraborti D, Sundar S, Fairlamb AH, Boelaert M, Picado A. Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in Bihar, India: a retrospective cohort study. PLoS Negl Trop Dis. 2015 Mar; 9(3):e0003518. PMID: 25730310; PMCID: PMC4346263.
    7. Perry M, Wyllie S, Prajapati V, Menten J, Raab A, Feldmann J, Chakraborti D, Sundar S, Boelaert M, Picado A, Fairlamb A. Arsenic, antimony, and Leishmania: has arsenic contamination of drinking water in India led to treatment- resistant kala-azar? Lancet. 2015 Feb 26; 385 Suppl 1:S80. PMID: 26312902.
      View in: PubMed
    8. Sola I, Castellà S, Viayna E, Galdeano C, Taylor MC, Gbedema SY, Pérez B, Clos MV, Jones DC, Fairlamb AH, Wright CW, Kelly JM, Muñoz-Torrero D. Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal-antiplasmodial activity. Bioorg Med Chem. 2015 Aug 15; 23(16):5156-67. PMID: 25678015.
      View in: PubMed
    9. Ong HB, Lee WS, Patterson S, Wyllie S, Fairlamb AH. Homoserine and quorum-sensing acyl homoserine lactones as alternative sources of threonine: a potential role for homoserine kinase in insect-stage Trypanosoma brucei. Mol Microbiol. 2015 Jan; 95(1):143-56. PMID: 25367138; PMCID: PMC4460637.
    10. Brand S, Norcross NR, Thompson S, Harrison JR, Smith VC, Robinson DA, Torrie LS, McElroy SP, Hallyburton I, Norval S, Scullion P, Stojanovski L, Simeons FR, van Aalten D, Frearson JA, Brenk R, Fairlamb AH, Ferguson MA, Wyatt PG, Gilbert IH, Read KD. Lead optimization of a pyrazole sulfonamide series of Trypanosoma brucei N-myristoyltransferase inhibitors: identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human African trypanosomiasis. J Med Chem. 2014 Dec 11; 57(23):9855-69. PMID: 25412409; PMCID: PMC4269550.
    11. Shameer S, Logan-Klumpler FJ, Vinson F, Cottret L, Merlet B, Achcar F, Boshart M, Berriman M, Breitling R, Bringaud F, Bütikofer P, Cattanach AM, Bannerman-Chukualim B, Creek DJ, Crouch K, de Koning HP, Denise H, Ebikeme C, Fairlamb AH, Ferguson MA, Ginger ML, Hertz-Fowler C, Kerkhoven EJ, Mäser P, Michels PA, Nayak A, Nes DW, Nolan DP, Olsen C, Silva-Franco F, Smith TK, Taylor MC, Tielens AG, Urbaniak MD, van Hellemond JJ, Vincent IM, Wilkinson SR, Wyllie S, Opperdoes FR, Barrett MP, Jourdan F. TrypanoCyc: a community-led biochemical pathways database for Trypanosoma brucei. Nucleic Acids Res. 2015 Jan; 43(Database issue):D637-44. PMID: 25300491; PMCID: PMC4384016.
    12. Roberts AJ, Torrie LS, Wyllie S, Fairlamb AH. Biochemical and genetic characterization of Trypanosoma cruzi N-myristoyltransferase. Biochem J. 2014 Apr 15; 459(2):323-32. PMID: 24444291; PMCID: PMC3969225.
    13. Hobley L, Kim SH, Maezato Y, Wyllie S, Fairlamb AH, Stanley-Wall NR, Michael AJ. Norspermidine is not a self-produced trigger for biofilm disassembly. Cell. 2014 Feb 13; 156(4):844-54. PMID: 24529384; PMCID: PMC3969229.
    14. Perry MR, Wyllie S, Raab A, Feldmann J, Fairlamb AH. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis. Proc Natl Acad Sci U S A. 2013 Dec 03; 110(49):19932-7. PMID: 24167266; PMCID: PMC3856816.
    15. Ong HB, Sienkiewicz N, Wyllie S, Patterson S, Fairlamb AH. Trypanosoma brucei (UMP synthase null mutants) are avirulent in mice, but recover virulence upon prolonged culture in vitro while retaining pyrimidine auxotrophy. Mol Microbiol. 2013 Oct; 90(2):443-55. PMID: 23980694; PMCID: PMC3868941.
    16. Patterson S, Wyllie S, Stojanovski L, Perry MR, Simeons FR, Norval S, Osuna-Cabello M, De Rycker M, Read KD, Fairlamb AH. The R enantiomer of the antitubercular drug PA-824 as a potential oral treatment for visceral Leishmaniasis. Antimicrob Agents Chemother. 2013 Oct; 57(10):4699-706. PMID: 23856774; PMCID: PMC3811480.
    17. De Rycker M, Hallyburton I, Thomas J, Campbell L, Wyllie S, Joshi D, Cameron S, Gilbert IH, Wyatt PG, Frearson JA, Fairlamb AH, Gray DW. Comparison of a high-throughput high-content intracellular Leishmania donovani assay with an axenic amastigote assay. Antimicrob Agents Chemother. 2013 Jul; 57(7):2913-22. PMID: 23571538; PMCID: PMC3697379.
    18. Nguyen S, Jones DC, Wyllie S, Fairlamb AH, Phillips MA. Allosteric activation of trypanosomatid deoxyhypusine synthase by a catalytically dead paralog. J Biol Chem. 2013 May 24; 288(21):15256-67. PMID: 23525104; PMCID: PMC3663545.
    19. Wyllie S, Patterson S, Fairlamb AH. Assessing the essentiality of Leishmania donovani nitroreductase and its role in nitro drug activation. Antimicrob Agents Chemother. 2013 Feb; 57(2):901-6. PMID: 23208716; PMCID: PMC3553740.
    20. De Rycker M, O'Neill S, Joshi D, Campbell L, Gray DW, Fairlamb AH. A static-cidal assay for Trypanosoma brucei to aid hit prioritisation for progression into drug discovery programmes. PLoS Negl Trop Dis. 2012; 6(11):e1932. PMID: 23209868; PMCID: PMC3510075.
    21. Jones DC, Alphey MS, Wyllie S, Fairlamb AH. Chemical, genetic and structural assessment of pyridoxal kinase as a drug target in the African trypanosome. Mol Microbiol. 2012 Oct; 86(1):51-64. PMID: 22857512; PMCID: PMC3470933.
    22. Fairlamb AH. Infectious disease: Genomics decodes drug action. Nature. 2012 Feb 08; 482(7384):167-9. PMID: 22318598.
      View in: PubMed
    23. Wyllie S, Patterson S, Stojanovski L, Simeons FR, Norval S, Kime R, Read KD, Fairlamb AH. The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. Sci Transl Med. 2012 Feb 01; 4(119):119re1. PMID: 22301556; PMCID: PMC3457684.
    24. Capes A, Patterson S, Wyllie S, Hallyburton I, Collie IT, McCarroll AJ, Stevens MF, Frearson JA, Wyatt PG, Fairlamb AH, Gilbert IH. Quinol derivatives as potential trypanocidal agents. Bioorg Med Chem. 2012 Feb 15; 20(4):1607-15. PMID: 22264753; PMCID: PMC3281193.
    25. Spinks D, Torrie LS, Thompson S, Harrison JR, Frearson JA, Read KD, Fairlamb AH, Wyatt PG, Gilbert IH. Design, synthesis and biological evaluation of Trypanosoma brucei trypanothione synthetase inhibitors. ChemMedChem. 2012 Jan 02; 7(1):95-106. PMID: 22162199; PMCID: PMC3320663.
    26. Brand S, Cleghorn LA, McElroy SP, Robinson DA, Smith VC, Hallyburton I, Harrison JR, Norcross NR, Spinks D, Bayliss T, Norval S, Stojanovski L, Torrie LS, Frearson JA, Brenk R, Fairlamb AH, Ferguson MA, Read KD, Wyatt PG, Gilbert IH. Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors. J Med Chem. 2012 Jan 12; 55(1):140-52. PMID: 22148754; PMCID: PMC3256935.
    27. Perry MR, Wyllie S, Prajapati VK, Feldmann J, Sundar S, Boelaert M, Fairlamb AH. Visceral leishmaniasis and arsenic: an ancient poison contributing to antimonial treatment failure in the Indian subcontinent? PLoS Negl Trop Dis. 2011 Sep; 5(9):e1227. PMID: 21980542; PMCID: PMC3181240.
    28. Patterson S, Alphey MS, Jones DC, Shanks EJ, Street IP, Frearson JA, Wyatt PG, Gilbert IH, Fairlamb AH. Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: discovery, synthesis, and characterization of their binding mode by protein crystallography. J Med Chem. 2011 Oct 13; 54(19):6514-30. PMID: 21851087; PMCID: PMC3188286.
    29. Smith VC, Cleghorn LA, Woodland A, Spinks D, Hallyburton I, Collie IT, Mok NY, Norval S, Brenk R, Fairlamb AH, Frearson JA, Read KD, Gilbert IH, Wyatt PG. Optimisation of the anti-Trypanosoma brucei activity of the opioid agonist U50488. ChemMedChem. 2011 Oct 04; 6(10):1832-40. PMID: 21834094; PMCID: PMC3229842.
    30. Fairlamb A, Cole S. Antimicrobial drug discovery. Future Microbiol. 2011 Jun; 6(6):601-2. PMID: 21707305.
      View in: PubMed
    31. Wyllie S, Fairlamb AH. Methylglyoxal metabolism in trypanosomes and leishmania. Semin Cell Dev Biol. 2011 May; 22(3):271-7. PMID: 21310261; PMCID: PMC3107426.
    32. Ong HB, Sienkiewicz N, Wyllie S, Fairlamb AH. Dissecting the metabolic roles of pteridine reductase 1 in Trypanosoma brucei and Leishmania major. J Biol Chem. 2011 Mar 25; 286(12):10429-38. PMID: 21239486; PMCID: PMC3060496.
    33. König J, Wyllie S, Wells G, Stevens MF, Wyatt PG, Fairlamb AH. Antitumor quinol PMX464 is a cytocidal anti-trypanosomal inhibitor targeting trypanothione metabolism. J Biol Chem. 2011 Mar 11; 286(10):8523-33. PMID: 21212280; PMCID: PMC3048735.
    34. Wyatt PG, Gilbert IH, Read KD, Fairlamb AH. Target validation: linking target and chemical properties to desired product profile. Curr Top Med Chem. 2011; 11(10):1275-83. PMID: 21401506; PMCID: PMC3182078.
    35. Baschong W, Wittlin S, Inglis KA, Fairlamb AH, Croft SL, Kumar TR, Fidock DA, Brun R. Triclosan is minimally effective in rodent malaria models. Nat Med. 2011 Jan; 17(1):33-4; author reply 34-5. PMID: 21217674.
      View in: PubMed
    36. Spinks D, Ong HB, Mpamhanga CP, Shanks EJ, Robinson DA, Collie IT, Read KD, Frearson JA, Wyatt PG, Brenk R, Fairlamb AH, Gilbert IH. Design, synthesis and biological evaluation of novel inhibitors of Trypanosoma brucei pteridine reductase 1. ChemMedChem. 2011 Feb 07; 6(2):302-8. PMID: 21275054; PMCID: PMC3047710.
    37. Walton JG, Jones DC, Kiuru P, Durie AJ, Westwood NJ, Fairlamb AH. Synthesis and evaluation of indatraline-based inhibitors for trypanothione reductase. ChemMedChem. 2011 Feb 07; 6(2):321-8. PMID: 21275055; PMCID: PMC3047706.
    38. Jones DC, Hallyburton I, Stojanovski L, Read KD, Frearson JA, Fairlamb AH. Identification of a ?-opioid agonist as a potent and selective lead for drug development against human African trypanosomiasis. Biochem Pharmacol. 2010 Nov 15; 80(10):1478-86. PMID: 20696141; PMCID: PMC3025325.
    39. Sienkiewicz N, Ong HB, Fairlamb AH. Trypanosoma brucei pteridine reductase 1 is essential for survival in vitro and for virulence in mice. Mol Microbiol. 2010 Aug; 77(3):658-71. PMID: 20545846; PMCID: PMC2916222.
    40. Wyllie S, Mandal G, Singh N, Sundar S, Fairlamb AH, Chatterjee M. Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates. Mol Biochem Parasitol. 2010 Oct; 173(2):162-4. PMID: 20553768; PMCID: PMC3428625.
    41. Sokolova AY, Wyllie S, Patterson S, Oza SL, Read KD, Fairlamb AH. Cross-resistance to nitro drugs and implications for treatment of human African trypanosomiasis. Antimicrob Agents Chemother. 2010 Jul; 54(7):2893-900. PMID: 20439607; PMCID: PMC2897277.
    42. Frearson JA, Brand S, McElroy SP, Cleghorn LA, Smid O, Stojanovski L, Price HP, Guther ML, Torrie LS, Robinson DA, Hallyburton I, Mpamhanga CP, Brannigan JA, Wilkinson AJ, Hodgkinson M, Hui R, Qiu W, Raimi OG, van Aalten DM, Brenk R, Gilbert IH, Read KD, Fairlamb AH, Ferguson MA, Smith DF, Wyatt PG. N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature. 2010 Apr 01; 464(7289):728-32. PMID: 20360736; PMCID: PMC2917743.
    43. Spinks D, Shanks EJ, Cleghorn LA, McElroy S, Jones D, James D, Fairlamb AH, Frearson JA, Wyatt PG, Gilbert IH. Investigation of trypanothione reductase as a drug target in Trypanosoma brucei. ChemMedChem. 2009 Dec; 4(12):2060-9. PMID: 19924760; PMCID: PMC2855869.
    44. Torrie LS, Wyllie S, Spinks D, Oza SL, Thompson S, Harrison JR, Gilbert IH, Wyatt PG, Fairlamb AH, Frearson JA. Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis. J Biol Chem. 2009 Dec 25; 284(52):36137-45. PMID: 19828449; PMCID: PMC2794729.
    45. Shanks EJ, Ong HB, Robinson DA, Thompson S, Sienkiewicz N, Fairlamb AH, Frearson JA. Development and validation of a cytochrome c-coupled assay for pteridine reductase 1 and dihydrofolate reductase. Anal Biochem. 2010 Jan 15; 396(2):194-203. PMID: 19748480; PMCID: PMC2789237.
    46. Jones DC, Ariza A, Chow WH, Oza SL, Fairlamb AH. Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi. Mol Biochem Parasitol. 2010 Jan; 169(1):12-9. PMID: 19747949; PMCID: PMC2789240.
    47. Patterson S, Jones DC, Shanks EJ, Frearson JA, Gilbert IH, Wyatt PG, Fairlamb AH. Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase. ChemMedChem. 2009 Aug; 4(8):1341-53. PMID: 19557802; PMCID: PMC2929374.
    48. Richardson JL, Nett IR, Jones DC, Abdille MH, Gilbert IH, Fairlamb AH. Improved tricyclic inhibitors of trypanothione reductase by screening and chemical synthesis. ChemMedChem. 2009 Aug; 4(8):1333-40. PMID: 19557801; PMCID: PMC2929371.
    49. Mpamhanga CP, Spinks D, Tulloch LB, Shanks EJ, Robinson DA, Collie IT, Fairlamb AH, Wyatt PG, Frearson JA, Hunter WN, Gilbert IH, Brenk R. One scaffold, three binding modes: novel and selective pteridine reductase 1 inhibitors derived from fragment hits discovered by virtual screening. J Med Chem. 2009 Jul 23; 52(14):4454-65. PMID: 19527033; PMCID: PMC2966039.
    50. Wyllie S, Oza SL, Patterson S, Spinks D, Thompson S, Fairlamb AH. Dissecting the essentiality of the bifunctional trypanothione synthetase-amidase in Trypanosoma brucei using chemical and genetic methods. Mol Microbiol. 2009 Nov; 74(3):529-40. PMID: 19558432; PMCID: PMC2784880.
    51. Holloway GA, Charman WN, Fairlamb AH, Brun R, Kaiser M, Kostewicz E, Novello PM, Parisot JP, Richardson J, Street IP, Watson KG, Baell JB. Trypanothione reductase high-throughput screening campaign identifies novel classes of inhibitors with antiparasitic activity. Antimicrob Agents Chemother. 2009 Jul; 53(7):2824-33. PMID: 19364854; PMCID: PMC2704697.
    52. Perez-Pineiro R, Burgos A, Jones DC, Andrew LC, Rodriguez H, Suarez M, Fairlamb AH, Wishart DS. Development of a novel virtual screening cascade protocol to identify potential trypanothione reductase inhibitors. J Med Chem. 2009 Mar 26; 52(6):1670-80. PMID: 19296695; PMCID: PMC2659691.
    53. Greig N, Wyllie S, Patterson S, Fairlamb AH. A comparative study of methylglyoxal metabolism in trypanosomatids. FEBS J. 2009 Jan; 276(2):376-86. PMID: 19076214; PMCID: PMC2702497.
    54. Oza SL, Chen S, Wyllie S, Coward JK, Fairlamb AH. ATP-dependent ligases in trypanothione biosynthesis--kinetics of catalysis and inhibition by phosphinic acid pseudopeptides. FEBS J. 2008 Nov; 275(21):5408-21. PMID: 18959765; PMCID: PMC2702004.
    55. Alphey MS, König J, Fairlamb AH. Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases. Biochem J. 2008 Sep 15; 414(3):375-81. PMID: 18522537; PMCID: PMC2552391.
    56. Sienkiewicz N, Jaroslawski S, Wyllie S, Fairlamb AH. Chemical and genetic validation of dihydrofolate reductase-thymidylate synthase as a drug target in African trypanosomes. Mol Microbiol. 2008 Jul; 69(2):520-33. PMID: 18557814; PMCID: PMC2610392.
    57. Gallo MB, Marques AS, Vieira PC, da Silva MF, Fernandes JB, Silva M, Guido RV, Oliva G, Thiemann OH, Albuquerque S, Fairlamb AH. Enzymatic inhibitory activity and trypanocidal effects of extracts and compounds from Siphoneugena densiflora O. Berg and Vitex polygama Cham. Z Naturforsch C. 2008 May-Jun; 63(5-6):371-82. PMID: 18669023; PMCID: PMC3428908.
    58. Fyfe PK, Oza SL, Fairlamb AH, Hunter WN. Leishmania trypanothione synthetase-amidase structure reveals a basis for regulation of conflicting synthetic and hydrolytic activities. J Biol Chem. 2008 Jun 20; 283(25):17672-80. PMID: 18420578; PMCID: PMC2427367.
    59. Stuart K, Brun R, Croft S, Fairlamb A, Gürtler RE, McKerrow J, Reed S, Tarleton R. Kinetoplastids: related protozoan pathogens, different diseases. J Clin Invest. 2008 Apr; 118(4):1301-10. PMID: 18382742; PMCID: PMC2276762.
    60. Wyllie S, Vickers TJ, Fairlamb AH. Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials. Antimicrob Agents Chemother. 2008 Apr; 52(4):1359-65. PMID: 18250189; PMCID: PMC2292513.
    61. Frearson JA, Wyatt PG, Gilbert IH, Fairlamb AH. Target assessment for antiparasitic drug discovery. Trends Parasitol. 2007 Dec; 23(12):589-95. PMID: 17962072; PMCID: PMC2979298.
    62. König J, Fairlamb AH. A comparative study of type I and type II tryparedoxin peroxidases in Leishmania major. FEBS J. 2007 Nov; 274(21):5643-58. PMID: 17922848; PMCID: PMC3430366.
    63. Mandal G, Wyllie S, Singh N, Sundar S, Fairlamb AH, Chatterjee M. Increased levels of thiols protect antimony unresponsive Leishmania donovani field isolates against reactive oxygen species generated by trivalent antimony. Parasitology. 2007 Nov; 134(Pt 12):1679-87. PMID: 17612420; PMCID: PMC3409873.
    64. Caffrey CR, Steverding D, Swenerton RK, Kelly B, Walshe D, Debnath A, Zhou YM, Doyle PS, Fafarman AT, Zorn JA, Land KM, Beauchene J, Schreiber K, Moll H, Ponte-Sucre A, Schirmeister T, Saravanamuthu A, Fairlamb AH, Cohen FE, McKerrow JH, Weisman JL, May BC. Bis-acridines as lead antiparasitic agents: structure-activity analysis of a discrete compound library in vitro. Antimicrob Agents Chemother. 2007 Jun; 51(6):2164-72. PMID: 17371810; PMCID: PMC1891397.
    65. Martyn DC, Jones DC, Fairlamb AH, Clardy J. High-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity. Bioorg Med Chem Lett. 2007 Mar 01; 17(5):1280-3. PMID: 17197182; PMCID: PMC3428910.
    66. Holloway GA, Baell JB, Fairlamb AH, Novello PM, Parisot JP, Richardson J, Watson KG, Street IP. Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening. Bioorg Med Chem Lett. 2007 Mar 01; 17(5):1422-7. PMID: 17194585; PMCID: PMC3428904.
    67. Greig N, Wyllie S, Vickers TJ, Fairlamb AH. Trypanothione-dependent glyoxalase I in Trypanosoma cruzi. Biochem J. 2006 Dec 01; 400(2):217-23. PMID: 16958620; PMCID: PMC1652828.
    68. Dawson A, Gibellini F, Sienkiewicz N, Tulloch LB, Fyfe PK, McLuskey K, Fairlamb AH, Hunter WN. Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate. Mol Microbiol. 2006 Sep; 61(6):1457-68. PMID: 16968221; PMCID: PMC1618733.
    69. Oza SL, Wyllie S, Fairlamb AH. Mapping the functional synthetase domain of trypanothione synthetase from Leishmania major. Mol Biochem Parasitol. 2006 Sep; 149(1):117-20. PMID: 16765464.
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    70. Wyllie S, Fairlamb AH. Refinement of techniques for the propagation of Leishmania donovani in hamsters. Acta Trop. 2006 Mar; 97(3):364-9. PMID: 16464432.
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    71. Ariza A, Vickers TJ, Greig N, Armour KA, Dixon MJ, Eggleston IM, Fairlamb AH, Bond CS. Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme. Mol Microbiol. 2006 Feb; 59(4):1239-48. PMID: 16430697.
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    72. Wickramasinghe SR, Inglis KA, Urch JE, Müller S, van Aalten DM, Fairlamb AH. Kinetic, inhibition and structural studies on 3-oxoacyl-ACP reductase from Plasmodium falciparum, a key enzyme in fatty acid biosynthesis. Biochem J. 2006 Jan 15; 393(Pt 2):447-57. PMID: 16225460; PMCID: PMC1360695.
    73. Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Microbiol Rev. 2006 Jan; 19(1):111-26. PMID: 16418526; PMCID: PMC1360270.
    74. Smith AT, Tucker-Samaras SD, Fairlamb AH, Sullivan WJ. MYST family histone acetyltransferases in the protozoan parasite Toxoplasma gondii. Eukaryot Cell. 2005 Dec; 4(12):2057-65. PMID: 16339723; PMCID: PMC1317489.
    75. Wyllie S, Fairlamb AH. Differential toxicity of antimonial compounds and their effects on glutathione homeostasis in a human leukaemia monocyte cell line. Biochem Pharmacol. 2006 Jan 12; 71(3):257-67. PMID: 16318845.
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    76. Hamilton CJ, Saravanamuthu A, Poupat C, Fairlamb AH, Eggleston IM. Time-dependent inhibitors of trypanothione reductase: analogues of the spermidine alkaloid lunarine and related natural products. Bioorg Med Chem. 2006 Apr 01; 14(7):2266-78. PMID: 16303308.
      View in: PubMed
    77. Ariyanayagam MR, Oza SL, Guther ML, Fairlamb AH. Phenotypic analysis of trypanothione synthetase knockdown in the African trypanosome. Biochem J. 2005 Oct 15; 391(Pt 2):425-32. PMID: 16008527; PMCID: PMC1276942.
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    169. el-Waer AF, Smith K, McKie JH, Benson T, Fairlamb AH, Douglas KT. The glutamyl binding site of trypanothione reductase from Crithidia fasciculata: enzyme kinetic properties of gamma-glutamyl-modified substrate analogues. Biochim Biophys Acta. 1993 Nov 10; 1203(1):93-8. PMID: 8105896.
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    170. Berger BJ, Carter NS, Fairlamb AH. Polyamine and pentamidine metabolism in African trypanosomes. Acta Trop. 1993 Sep; 54(3-4):215-24. PMID: 7902659.
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    171. Zhang Y, Bailey S, Naismith JH, Bond CS, Habash J, McLaughlin P, Papiz MZ, Borges A, Cunningham M, Fairlamb AH, et al. Trypanosoma cruzi trypanothione reductase. Crystallization, unit cell dimensions and structure solution. J Mol Biol. 1993 Aug 20; 232(4):1217-20. PMID: 8371273.
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    172. Berger BJ, Fairlamb AH. Cytochrome P450 in trypanosomatids. Biochem Pharmacol. 1993 Jul 06; 46(1):149-57. PMID: 8347125.
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    173. Bailey S, Smith K, Fairlamb AH, Hunter WN. Substrate interactions between trypanothione reductase and N1-glutathionylspermidine disulphide at 0.28-nm resolution. Eur J Biochem. 1993 Apr 01; 213(1):67-75. PMID: 8477734.
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    174. Carter NS, Fairlamb AH. Arsenical-resistant trypanosomes lack an unusual adenosine transporter. Nature. 1993 Jan 14; 361(6408):173-6. PMID: 8421523.
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    175. Aboagye-Kwarteng T, Smith K, Fairlamb AH. Molecular characterization of the trypanothione reductase gene from Crithidia fasciculata and Trypanosoma brucei: comparison with other flavoprotein disulphide oxidoreductases with respect to substrate specificity and catalytic mechanism. Mol Microbiol. 1992 Nov; 6(21):3089-99. PMID: 1453951.
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    176. Hunter WN, Bailey S, Habash J, Harrop SJ, Helliwell JR, Aboagye-Kwarteng T, Smith K, Fairlamb AH. Active site of trypanothione reductase. A target for rational drug design. J Mol Biol. 1992 Sep 05; 227(1):322-33. PMID: 1522596.
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    177. Benson TJ, McKie JH, Garforth J, Borges A, Fairlamb AH, Douglas KT. Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures. Biochem J. 1992 Aug 15; 286 ( Pt 1):9-11. PMID: 1355650; PMCID: PMC1133010.
    178. Fairlamb AH, Smith K, Hunter KJ. The interaction of arsenical drugs with dihydrolipoamide and dihydrolipoamide dehydrogenase from arsenical resistant and sensitive strains of Trypanosoma brucei brucei. Mol Biochem Parasitol. 1992 Jul; 53(1-2):223-31. PMID: 1501642.
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    179. Fairlamb AH, Carter NS, Cunningham M, Smith K. Characterisation of melarsen-resistant Trypanosoma brucei brucei with respect to cross-resistance to other drugs and trypanothione metabolism. Mol Biochem Parasitol. 1992 Jul; 53(1-2):213-22. PMID: 1501641.
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    180. Smith K, Nadeau K, Bradley M, Walsh C, Fairlamb AH. Purification of glutathionylspermidine and trypanothione synthetases from Crithidia fasciculata. Protein Sci. 1992 Jul; 1(7):874-83. PMID: 1304372; PMCID: PMC2142158.
    181. Komuniecki R, Bruchhaus I, Ilg T, Wilson K, Zhang Y, Fairlamb AH. Purification of glutathione reductase from muscle of the adult parasitic nematode Ascaris suum. Mol Biochem Parasitol. 1992 Apr; 51(2):331-3. PMID: 1574090.
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    182. Fairlamb AH, Cerami A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol. 1992; 46:695-729. PMID: 1444271.
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    183. Berger BJ, Fairlamb AH. Interactions between immunity and chemotherapy in the treatment of the trypanosomiases and leishmaniases. Parasitology. 1992; 105 Suppl:S71-8. PMID: 1308932.
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    184. el-Waer A, Douglas KT, Smith K, Fairlamb AH. Synthesis of N-benzyloxycarbonyl-L-cysteinylglycine 3-dimethylaminopropylamide disulfide: a cheap and convenient new assay for trypanothione reductase. Anal Biochem. 1991 Oct; 198(1):212-6. PMID: 1789428.
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    185. Smith K, Opperdoes FR, Fairlamb AH. Subcellular distribution of trypanothione reductase in bloodstream and procyclic forms of Trypanosoma brucei. Mol Biochem Parasitol. 1991 Sep; 48(1):109-12. PMID: 1779986.
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    186. Hunter KJ, Strobos CA, Fairlamb AH. Inhibition of polyamine biosynthesis in Crithidia fasciculata by D,L-alpha-difluoromethylornithine and D,L-alpha-difluoromethylarginine. Mol Biochem Parasitol. 1991 May; 46(1):35-43. PMID: 1852175.
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    187. Hunter KJ, Strobos CA, Fairlamb AH. The interaction of trypanocidal drugs with polyamine and trypanothione metabolism. Biochem Soc Trans. 1990 Dec; 18(6):1094-6. PMID: 2088818.
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    188. Hunter WN, Smith K, Derewenda Z, Harrop SJ, Habash J, Islam MS, Helliwell JR, Fairlamb AH. Initiating a crystallographic study of trypanothione reductase. J Mol Biol. 1990 Nov 20; 216(2):235-7. PMID: 2254926.
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    189. Hunter KJ, Fairlamb AH. Separation and quantitation of the polyamine biosynthesis inhibitor D,L-alpha-difluoromethylarginine and other guanidine-containing compounds by high-performance liquid chromatography. Anal Biochem. 1990 Nov 01; 190(2):281-5. PMID: 2291471.
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    190. Taylor MC, Kelly JM, Fairlamb AH, Miles MA. The trypanothione reductase gene of Leishmania donovani. Biochem Soc Trans. 1990 Oct; 18(5):869-70. PMID: 2083703.
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    191. Fairlamb AH. Trypanothione metabolism and rational approaches to drug design. Biochem Soc Trans. 1990 Oct; 18(5):717-20. PMID: 2083656.
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    192. Fairlamb AH. Future prospects for the chemotherapy of human trypanosomiasis. 1. Novel approaches to the chemotherapy of trypanosomiasis. Trans R Soc Trop Med Hyg. 1990 Sep-Oct; 84(5):613-7. PMID: 2278053.
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    193. Henderson GB, Yamaguchi M, Novoa L, Fairlamb AH, Cerami A. Biosynthesis of the trypanosomatid metabolite trypanothione: purification and characterization of trypanothione synthetase from Crithidia fasciculata. Biochemistry. 1990 Apr 24; 29(16):3924-9. PMID: 2354163.
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    194. Fairlamb AH, Henderson GB, Cerami A. Trypanothione is the primary target for arsenical drugs against African trypanosomes. Proc Natl Acad Sci U S A. 1989 Apr; 86(8):2607-11. PMID: 2704738; PMCID: PMC286966.
    195. Fairlamb AH. Novel biochemical pathways in parasitic protozoa. Parasitology. 1989; 99 Suppl:S93-112. PMID: 2682488.
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    196. Henderson GB, Ulrich P, Fairlamb AH, Rosenberg I, Pereira M, Sela M, Cerami A. "Subversive" substrates for the enzyme trypanothione disulfide reductase: alternative approach to chemotherapy of Chagas disease. Proc Natl Acad Sci U S A. 1988 Aug; 85(15):5374-8. PMID: 3135548; PMCID: PMC281759.
    197. Shim H, Fairlamb AH. Levels of polyamines, glutathione and glutathione-spermidine conjugates during growth of the insect trypanosomatid Crithidia fasciculata. J Gen Microbiol. 1988 Mar; 134(3):807-17. PMID: 3183621.
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    198. Fairlamb AH. The role of glutathionylspermidine and trypanothione in regulation of intracellular spermidine levels during growth of Crithidia fasciculata. Adv Exp Med Biol. 1988; 250:667-74. PMID: 3255244.
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    199. Bellofatto V, Fairlamb AH, Henderson GB, Cross GA. Biochemical changes associated with alpha-difluoromethylornithine uptake and resistance in Trypanosoma brucei. Mol Biochem Parasitol. 1987 Oct; 25(3):227-38. PMID: 3122042.
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    200. Henderson GB, Fairlamb AH. Trypanothione metabolism: a chemotherapeutic target in trypanosomatids. Parasitol Today. 1987 Oct; 3(10):312-5. PMID: 15462875.
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    201. Henderson GB, Fairlamb AH, Ulrich P, Cerami A. Substrate specificity of the flavoprotein trypanothione disulfide reductase from Crithidia fasciculata. Biochemistry. 1987 Jun 02; 26(11):3023-7. PMID: 3607007.
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    202. Fairlamb AH, Henderson GB, Bacchi CJ, Cerami A. In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei. Mol Biochem Parasitol. 1987 Jun; 24(2):185-91. PMID: 3114634.
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    203. Henderson GB, Fairlamb AH, Cerami A. Trypanothione dependent peroxide metabolism in Crithidia fasciculata and Trypanosoma brucei. Mol Biochem Parasitol. 1987 May; 24(1):39-45. PMID: 3614271.
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    204. Krauth-Siegel RL, Enders B, Henderson GB, Fairlamb AH, Schirmer RH. Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme. Eur J Biochem. 1987 Apr 01; 164(1):123-8. PMID: 3549299.
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    205. Fairlamb AH, Henderson GB, Cerami A. The biosynthesis of trypanothione and N1-glutathionylspermidine in Crithidia fasciculata. Mol Biochem Parasitol. 1986 Dec; 21(3):247-57. PMID: 3807945.
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    206. Shames SL, Fairlamb AH, Cerami A, Walsh CT. Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulfide-containing flavoprotein reductases. Biochemistry. 1986 Jun 17; 25(12):3519-26. PMID: 3718941.
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    207. Fairlamb AH, Warhurst DC, Peters W. An improved technique for the cultivation of Plasmodium falciparum in vitro without daily medium change. Ann Trop Med Parasitol. 1985 Aug; 79(4):379-84. PMID: 3907558.
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    208. Rifkin MR, Fairlamb AH. Transport of ethanolamine and its incorporation into the variant surface glycoprotein of bloodstream forms of Trypanosoma brucei. Mol Biochem Parasitol. 1985 Jun; 15(3):245-56. PMID: 4033688.
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    209. Fairlamb AH, Blackburn P, Ulrich P, Chait BT, Cerami A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science. 1985 Mar 22; 227(4693):1485-7. PMID: 3883489.
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    210. Fairlamb AH, Cerami A. Identification of a novel, thiol-containing co-factor essential for glutathione reductase enzyme activity in trypanosomatids. Mol Biochem Parasitol. 1985 Feb; 14(2):187-98. PMID: 3990705.
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    211. Fairlamb AH, Paul F, Warhurst DC. A simple magnetic method for the purification of malarial pigment. Mol Biochem Parasitol. 1984 Jul; 12(3):307-12. PMID: 10610436.
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    212. Hotez PJ, Le Trang N, Fairlamb AH, Cerami A. Lipoprotein lipase suppression in 3T3-L1 cells by a haematoprotozoan-induced mediator from peritoneal exudate cells. Parasite Immunol. 1984 May; 6(3):203-9. PMID: 6377200.
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    213. Fairlamb AH, Bowman IB. Uptake of the trypanocidal drug suramin by bloodstream forms of Trypanosoma brucei and its effect on respiration and growth rate in vivo. Mol Biochem Parasitol. 1980 Oct; 1(6):315-33. PMID: 6108510.
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    214. Fairlamb AH, Bowman IB. An improved method for the estimation of suramin in plasma and trypanosome samples. Mol Biochem Parasitol. 1980 Oct; 1(6):307-13. PMID: 6108509.
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    215. Fairlamb AH, Bowman IB. Trypanosoma brucei: maintenance of concentrated suspensions of bloodstream trypomastigotes in vitro using continuous dialysis for measurement of endocytosis. Exp Parasitol. 1980 Jun; 49(3):366-80. PMID: 7371738.
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    216. Fairlamb AH, Weislogel PO, Hoeijmakers JH, Borst P. Isolation and characterization of kinetoplast DNA from bloodstream form of Trypanosoma brucei. J Cell Biol. 1978 Feb; 76(2):293-309. PMID: 10605439; PMCID: PMC2109978.
    217. Fairlamb AH, Bowman IB. Trypanosoma brucei: suramin and other trypanocidal compounds' effects on sn-glycerol-3-phosphate oxidase. Exp Parasitol. 1977 Dec; 43(2):353-61. PMID: 598447.
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    218. Weislogel PO, Hoeijmakers JH, Fairlamb AH, Kleisen CM, Borst P. Characterization of kinetoplast DNA networks from the insect trypanosome Crithidia luciliae. Biochim Biophys Acta. 1977 Sep 20; 478(2):167-79. PMID: 901791.
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    219. Fairlamb AH, Opperdoes FR, Borst P. New approach to screening drugs for activity against African trypanosomes. Nature. 1977 Jan 20; 265(5591):270-1. PMID: 834274.
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    220. Fairlamb AH, Bowman IB. Cell disruption and subcellular fractionation of Trypanosoma brucei. Trans R Soc Trop Med Hyg. 1974; 68(4):275. PMID: 4417067.
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