Discovery of a new class of inhibitors for the protein arginine deiminase type 4 (PAD4) by structure-based virtual screening

详细信息    查看全文

• 作者：Chian Ying Teo (1)
  Steven Shave (2)
  Adam Leow Thean Chor (3)
  Abu Bakar Salleh (4)
  Mohd Basyaruddin Bin Abdul Rahman (1)
  Malcolm D Walkinshaw (2)
  Bimo A Tejo (1)
  
• 刊名：BMC Bioinformatics
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：13
• 期：17-supp
• 全文大小：816KB
• 参考文献：1. Wegner N, Lundberg K, Kinloch A, Fisher B, Malmstrom V, Feldmann M, Venables PJ: Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. / Immunol Rev 2010,233(1):34鈥?4. CrossRef
  2. Akil M, Amos RS: ABC of rheumatology. Rheumatoid arthritis--I: clinical features and diagnosis. / BMJ 1995,310(6979):587鈥?90. CrossRef
  3. Finesilver AG: Newer approaches to the treatment of rheumatoid arthritis. / WMJ 2003,102(7):34鈥?7.
  4. Aceves-Avila FJ, Medina F, Fraga A: The antiquity of rheumatoid arthritis: a reappraisal. / J Rheumatol 2001,28(4):751鈥?57.
  5. Rothschild BM, Coppa A, Petrone PP: "Like a virgin": absence of rheumatoid arthritis and treponematosis, good sanitation and only rare gout in Italy prior to the 15th century. / Reumatismo 2004,56(1):61鈥?6.
  6. Landre-Beauvais AJ: The first description of rheumatoid arthritis. Unabridged text of the doctoral dissertation presented in 1800. / Joint Bone Spine 2001,68(2):130鈥?43. 47-5">CrossRef
  7. Storey GD: Alfred Baring Garrod (1819鈥?907). [40/10/1189.full" class="a-plus-plus">http://rheumatology.oxfordjournals.org/content/40/10/1189.full] / Rheumatology 2001,40(10):1189鈥?190. 40.10.1189">CrossRef
  8. Suzuki A, Yamada R, Yamamoto K: Citrullination by peptidylarginine deiminase in rheumatoid arthritis. / Ann N Y Acad Sci 2007, 1108:323鈥?39. 422.034">CrossRef
  9. Conrad K, Roggenbuck D, Reinhold D, Dorner T: Profiling of rheumatoid arthritis associated autoantibodies. / Autoimmun Rev 2010,9(6):431鈥?35. CrossRef
  10. van Boekel MA, Vossenaar ER, van den Hoogen FH, van Venrooij WJ: Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. / Arthritis Res 2002,4(2):87鈥?3. CrossRef
  11. Steiner G, Smolen J: Autoantibodies in rheumatoid arthritis and their clinical significance. / Arthritis Res 2002,4(Suppl 2):S1鈥?. CrossRef
  12. Schellekens GA, Visser H, de Jong BA, van den Hoogen FH, Hazes JM, Breedveld FC, van Venrooij WJ: The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. / Arthritis Rheum 2000,43(1):155鈥?63. 43:1<155::AID-ANR20>3.0.CO;2-3">CrossRef
  13. Kang CP, Lee HS, Ju H, Cho H, Kang C, Bae SC: A functional haplotype of the PADI4 gene associated with increased rheumatoid arthritis susceptibility in Koreans. / Arthritis Rheum 2006,54(1):90鈥?6. CrossRef
  14. Barton A, Bowes J, Eyre S, Spreckley K, Hinks A, John S, Worthington J: A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population. / Arthritis Rheum 2004,50(4):1117鈥?121. CrossRef
  15. Fan LY, Wang WJ, Wang Q, Zong M, Yang L, Zhang H, Sun LS, Lu TB, Han J: A functional haplotype and expression of the PADI4 gene associated with increased rheumatoid arthritis susceptibility in Chinese. / Tissue Antigens 2008,72(5):469鈥?73. CrossRef
  16. Burr ML, Naseem H, Hinks A, Eyre S, Gibbons LJ, Bowes J, Wilson AG, Maxwell J, Morgan AW, Emery P, / et al.: PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian population. / Ann Rheum Dis 2010,69(4):666鈥?70. 4">CrossRef
  17. Iwamoto T, Ikari K, Nakamura T, Kuwahara M, Toyama Y, Tomatsu T, Momohara S, Kamatani N: Association between PADI4 and rheumatoid arthritis: a meta-analysis. / Rheumatology (Oxford) 2006,45(7):804鈥?07. CrossRef
  18. Chang X, Zhao Y, Sun S, Zhang Y, Zhu Y: The expression of PADI4 in synovium of rheumatoid arthritis. / Rheumatol Int 2009,29(12):1411鈥?416. CrossRef
  19. Smolen JS, Steiner G: Therapeutic strategies for rheumatoid arthritis. / Nat Rev Drug Discov 2003,2(6):473鈥?88. CrossRef
  20. Anderson AC: Structure-based functional design of drugs: from target to lead compound. / Methods Mol Biol 2012, 823:359鈥?66. CrossRef
  21. Taylor P, Blackburn E, Sheng YG, Harding S, Hsin KY, Kan D, Shave S, Walkinshaw MD: Ligand discovery and virtual screening using the program LIDAEUS. / Br J Pharmacol 2008,153(Suppl 1):S55鈥?7.
  22. Makino T, Skretas G, Kang TH, Georgiou G: Comprehensive engineering of Escherichia coli for enhanced expression of IgG antibodies. / Metab Eng 2011,13(2):241鈥?51. CrossRef
  23. Studier FW: Protein production by auto-induction in high density shaking cultures. / Protein Expr Purif 2005,41(1):207鈥?34. CrossRef
  24. Takahara H, Okamoto H, Sugawara K: Affinity chromatography of peptidylarginine deiminase from rabbit skeletal muscle on a column of soybean trypsin inhibitor (Kunitz)-Sepharose. / J Biochem 1986,99(5):1417鈥?424.
  25. Goodsell DS, Morris GM, Olson AJ: Automated docking of flexible ligands: applications of AutoDock. / J Mol Recognit 1996,9(1):1鈥?. 41>3.0.CO;2-6">CrossRef
  26. Lim SV, Rahman MB, Tejo BA: Structure-based and ligand-based virtual screening of novel methyltransferase inhibitors of the dengue virus. / BMC Bioinformatics 2011,12(Suppl 13):S24. 471-2105-12-S13-S24">CrossRef
  27. Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, Sato M: Structural basis for Ca(2+)-induced activation of human PAD4. / Nat Struct Mol Biol 2004,11(8):777鈥?83. CrossRef
  28. Kearney PL, Bhatia M, Jones NG, Yuan L, Glascock MC, Catchings KL, Yamada M, Thompson PR: Kinetic characterization of protein arginine deiminase 4: a transcriptional corepressor implicated in the onset and progression of rheumatoid arthritis. / Biochemistry 2005,44(31):10570鈥?0582. CrossRef
  29. Galkin A, Lu X, Dunaway-Mariano D, Herzberg O: Crystal structures representing the Michaelis complex and the thiouronium reaction intermediate of Pseudomonas aeruginosa arginine deiminase. / J Biol Chem 2005,280(40):34080鈥?4087. 4/jbc.M505471200">CrossRef
  30. Das K, Butler GH, Kwiatkowski V, Clark AD Jr, Yadav P, Arnold E: Crystal structures of arginine deiminase with covalent reaction intermediates; implications for catalytic mechanism. / Structure 2004,12(4):657鈥?67. 4.02.017">CrossRef
  31. Murray-Rust J, Leiper J, McAlister M, Phelan J, Tilley S, Santa Maria J, Vallance P, McDonald N: Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase. / Nat Struct Biol 2001,8(8):679鈥?83. CrossRef
  32. Shirai H, Blundell TL, Mizuguchi K: A novel superfamily of enzymes that catalyze the modification of guanidino groups. / Trends Biochem Sci 2001,26(8):465鈥?68. 4(01)01906-5">CrossRef
  33. Knuckley B, Bhatia M, Thompson PR: Protein arginine deiminase 4: evidence for a reverse protonation mechanism. / Biochemistry 2007,46(22):6578鈥?587. CrossRef
  34. Luo Y, Arita K, Bhatia M, Knuckley B, Lee YH, Stallcup MR, Sato M, Thompson PR: Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization. / Biochemistry 2006,45(39):11727鈥?1736. CrossRef
  35. Luo Y, Knuckley B, Lee YH, Stallcup MR, Thompson PR: A fluoroacetamidine-based inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. / J Am Chem Soc 2006,128(4):1092鈥?093. CrossRef
  36. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. / Adv Drug Deliv Rev 2001,46(1鈥?):3鈥?6. 409X(00)00129-0">CrossRef
  37. Leatherbarrow RJ: / GraFit Version 7. 7.0th edition. Horley, UK: Erithacus Software Limited; 2009.
  38. Subramaniam S, Mehrotra M, Gupta D: Virtual high throughput screening (vHTS)--a perspective. / Bioinformation 2008,3(1):14鈥?7. 4">CrossRef
  39. Schapira M, Raaka BM, Samuels HH, Abagyan R: Rational discovery of novel nuclear hormone receptor antagonists. / Proc Natl Acad Sci USA 2000,97(3):1008鈥?013. CrossRef
  40. Vangrevelinghe E, Zimmermann K, Schoepfer J, Portmann R, Fabbro D, Furet P: Discovery of a potent and selective protein kinase CK2 inhibitor by high-throughput docking. / J Med Chem 2003,46(13):2656鈥?662. CrossRef
  41. Starcevic S, Turk S, Brus B, Cesar J, Lanisnik Rizner T, Gobec S: Discovery of highly potent, nonsteroidal 17beta-hydroxysteroid dehydrogenase type 1 inhibitors by virtual high-throughput screening. / J Steroid Biochem Mol Biol 2008,127(3鈥?):255鈥?61. CrossRef
  42. Wang D, Wang F, Tan Y, Dong L, Chen L, Zhu W, Wang H: Discovery of potent small molecule inhibitors of DYRK1A by structure-based virtual screening and bioassay. / Bioorg Med Chem Lett 2011,22(1):168鈥?71. 43">CrossRef
  43. Yang Y, Moir E, Kontopidis G, Taylor P, Wear MA, Malone K, Dunsmore CJ, Page AP, Turner NJ, Walkinshaw MD: Structure-based discovery of a family of synthetic cyclophilin inhibitors showing a cyclosporin-A phenotype in Caenorhabditis elegans. / Biochem Biophys Res Commun 2007,363(4):1013鈥?019. CrossRef
  44. Lahana R: How many leads from HTS? / Drug Discov Today 1999,4(10):447鈥?48. 446(99)01393-8">CrossRef
  45. Wu SY, McNae I, Kontopidis G, McClue SJ, McInnes C, Stewart KJ, Wang S, Zheleva DI, Marriage H, Lane DP, / et al.: Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop. / Structure 2003,11(4):399鈥?10. CrossRef
  46. Knuckley B, Luo Y, Thompson PR: Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors. / Bioorg Med Chem 2008,16(2):739鈥?45. CrossRef
  47. Knuckley B, Jones JE, Bachovchin DA, Slack J, Causey CP, Brown SJ, Rosen H, Cravatt BF, Thompson PR: A fluopol-ABPP HTS assay to identify PAD inhibitors. / Chem Commun (Camb) 2010,46(38):7175鈥?177. 4d">CrossRef
  48. Causey CP, Jones JE, Slack JL, Kamei D, Jones LE, Subramanian V, Knuckley B, Ebrahimi P, Chumanevich AA, Luo Y, / et al.: The development of N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l-ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-l-ornithine amide (o-Cl-amidine) as second generation protein arginine deiminase (PAD) inhibitors. / J Med Chem 2011,54(19):6919鈥?935. CrossRef
  49. Jones JE, Slack JL, Fang P, Zhang X, Subramanian V, Causey CP, Coonrod SA, Guo M, Thompson PR: Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors. / ACS Chem Biol 2012,7(1):160鈥?65. CrossRef
  50. Bohlmann F, Fritz G: Synthese des racemats eines seco-furoeremophilans aus euryops hebecarpus [1]. / Tetrahedron Letters 1981,22(48):4803鈥?806. 40-4039(01)92347-0">CrossRef
  51. Zeni G, Ludtke DS, Nogueira CW, Panatieri RB, Braga AL, Silveira CC, Stefani HlA, Rocha JBT: New acetylenic furan derivatives: synthesis and anti-inflammatory activity. / Tetrahedron Letters 2001,42(51):8927鈥?930. 40-4039(01)01984-0">CrossRef
  52. Closse A, Haefliger W, Hauser D, Gubler HU, Dewald B, Baggiolini M: 2,3-Dihydrobenzofuran-2-ones: a new class of highly potent anti-inflammatory agents. / J Med Chem 1981,24(12):1465鈥?471. 44a019">CrossRef
  53. Wakimoto T, Kondo H, Nii H, Kimura K, Egami Y, Oka Y, Yoshida M, Kida E, Ye Y, Akahoshi S, / et al.: Furan fatty acid as an anti-inflammatory component from the green-lipped mussel Perna canaliculus. / Proc Natl Acad Sci USA 2011,108(42):17533鈥?7537. CrossRef
  54. Pandey Y, Sharma PK, Kumar N, Singh A: Biological activities of thiazolidine - a review. [http://www.cpronline.in/PDF1/CPR%201(2),%202011,%20192-196.%20(18).pdf] / Int J PharmTech Res 2011,3(2):980鈥?85.
  55. Missbach M, Jagher B, Sigg I, Nayeri S, Carlberg C, Wiesenberg I: Thiazolidine diones, specific ligands of the nuclear receptor retinoid Z receptor/retinoid acid receptor-related orphan receptor alpha with potent antiarthritic activity. / J Biol Chem 1996,271(23):13515鈥?3522. 4/jbc.271.23.13515">CrossRef
  56. Ma L, Xie C, Ma Y, Liu J, Xiang M, Ye X, Zheng H, Chen Z, Xu Q, Chen T, / et al.: Synthesis and biological evaluation of novel 5-benzylidenethiazolidine-2,4-dione derivatives for the treatment of inflammatory diseases. / J Med Chem 2011,54(7):2060鈥?068. 4">CrossRef
  57. Stierand K, Rarey M: From modeling to medicinal chemistry: automatic generation of two-dimensional complex diagrams. / ChemMedChem 2007,2(6):853鈥?60. CrossRef
  58. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. [http://www.sciencedirect.com/science/article/pii/0003269776905273] / Anal Biochem 1976, 72:248鈥?54. CrossRef
  
• 作者单位：Chian Ying Teo (1)
  Steven Shave (2)
  Adam Leow Thean Chor (3)
  Abu Bakar Salleh (4)
  Mohd Basyaruddin Bin Abdul Rahman (1)
  Malcolm D Walkinshaw (2)
  Bimo A Tejo (1)
  
  1. Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Malaysia
  2. Structural Biochemistry Group, The University of Edinburgh, Michael Swann Building, King鈥檚 Buildings, Edinburgh, EH9 3JR, UK
  3. Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Malaysia
  4. Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Malaysia
  
• ISSN：1471-2105

文摘

Background Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology. Anticitrullinated protein autoantibody has been documented as a highly specific autoantibody associated with RA. Protein arginine deiminase type 4 (PAD4) is the enzyme responsible for catalyzing the conversion of peptidylarginine into peptidylcitrulline. PAD4 is a new therapeutic target for RA treatment. In order to search for inhibitors of PAD4, structure-based virtual screening was performed using LIDAEUS (Ligand discovery at Edinburgh university). Potential inhibitors were screened experimentally by inhibition assays. Results Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC50 values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment. Conclusion Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.