Inhibition of human Transthyretin aggregation by non-steroidal anti-inflammatory compounds: A structural and thermodynamic analysis

International Journal of Molecular Sciences

Volumn 14, Issue 3, 2013, Pages 5284-5311

  Sant'Anna, Ricardo O ^a   Braga, Carolina A ^a   Polikarpov, Igor ^b   Ventura, Salvador ^c   Lima, Luis Mauricio T R ^a,d   Foguel, Debora ^a  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

^b UNIVERSITY OF SÃO PAULO   (Brazil)

^c UNIVERSITY OF BARCELONA   (Spain)

^d INSTITUTO NACIONAL DE METROLOGIA   (Brazil)

Author keywords

Crystallography; High hydrostatic pressure; Inhibitors; Protein aggregation; Transthyretin

Indexed keywords

ACID; DICLOFENAC; INDOMETACIN; LEUCINE; LUMIRACOXIB; NONSTEROID ANTIINFLAMMATORY AGENT; OLIGOMER; PREALBUMIN; PROLINE; SOLUBLE OLIGOMER; SULINDAC; TETRAMER; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; DRUG EFFICACY; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; HIGH HYDROSTATIC PRESSURE; HUMAN; HUMAN CELL; HYDROSTATIC PRESSURE; LIGAND BINDING; PROTEIN AGGREGATION; PROTEIN AGGREGATION INHIBITION; PROTEIN MODIFICATION; PROTEIN STABILITY; PROTEIN TARGETING; STRUCTURE ANALYSIS; THERMODYNAMICS; TOXICITY TESTING; WILD TYPE;

EID: 84875073880     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms14035284     Document Type: Article

References (72)

1. Gonzalez, G.; Offord, R.E. The subunit structure of prealbumin. Biochem. J. 1971, 125, 309-317.
2. Blake, C.C.F.; Geisow, M.J.; Oatley, S.J.; Rérat, B.; Rérat, C. Structure of prealbumin: Secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 Å. J. Mol. Biol. 1978, 121, 339-356.
3. Palaninathan, S.K. Nearly 200 X-ray crystal structures of transthyretin: What do they tell us about this protein and the design of drugs for TTR amyloidoses? Curr. Med. Chem. 2012, 19, 2324-2342.
4. Nilsson, S.F.; Rask, L.; Peterson, P.A. Studies on thyroid hormone-binding proteins. II. Binding of thyroid hormones, retinol-binding protein, and fluorescent probes to prealbumin and effects of thyroxine on prealbumin subunit self association. J. Biol. Chem. 1975, 250, 8554-8563.
5. Miroy, G.J.; Lai, Z.; Lashuel, H.A.; Peterson, S.A.; Strang, C.; Kelly, J.W. Inhibiting transthyretin amyloid fibril formation via protein stabilization. Proc. Natl. Acad. Sci. USA 1996, 93, 15051-15056.
6. Peterson, S.A.; Klabunde, T.; Lashuel, H.A.; Purkey, H.; Sacchettini, J.C.; Kelly, J.W. Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc. Natl. Acad. Sci. USA 1998, 95, 12956-12960.
7. Klabunde, T.; Petrassi, H.M.; Oza, V.B.; Raman, P.; Kelly, J.W.; Sacchettini, J.C. Rational design of potent human transthyretin amyloid disease inhibitors. Nat. Struct. Biol. 2000, 7, 312-321.
8. Miller, S.R.; Sekijima, Y.; Kelly, J.W. Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab. Invest. 2004, 84, 545-552.
9. Tojo, K.; Sekijima, Y.; Kelly, J.W.; Ikeda, S. Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis. Neurosci. Res. 2006, 56, 441-449.
10. Mairal, T.; Nieto, J.; Pinto, M.; Almeida, M.R.; Gales, L.; Ballesteros, A.; Barluenga, J.; Pérez, J.J.; Vázquez, J.T.; Centeno, N.B.; et al. Iodine atoms: A new molecular feature for the design of potent transthyretin fibrillogenesis inhibitors. PLoS One 2009, 4, e4124.
11. Ferreira, N.; Saraiva, M.J.; Almeida, M.R. Natural polyphenols inhibit different steps of the process of transthyretin (TTR) amyloid fibril formation. FEBS Lett. 2011, 585, 2424-2430.
12. Ferreira, N.; Saraiva, M.J.; Almeida, M.R. Natural polyphenols as modulators of TTR amyloidogenesis: In vitro and in vivo evidences towards therapy. Amyloid 2012, 19, 39-42.
13. Ferreira, N.; Santos, S.A.O.; Domingues, M.R.M.; Saraiva, M.J.; Almeida, M.R. Dietary curcumin counteracts extracellular transthyretin deposition: Insights on the mechanism of amyloid inhibition. Biochim. Biophys. Acta 2013, 1832, 39-45.
14. Ramirez-Alvarado, M.; Kelly, J.W.; Dobson, C.M. In Protein Misfolding Diseases: Current and Emerging Principles and Therapies; Ramirez-Alvarado, M., Kelly, J.W., Dobson, C.M., Eds.; Wiley Series in Protein and Peptide Science; Wiley: Malden, MA, USA, 2011.
15. Saraiva, M.J.; Magalhaes, J.; Ferreira, N.; Almeida, M.R. Transthyretin deposition in familial amyloidotic polyneuropathy. Curr. Med. Chem. 2012, 19, 2304-2311.
16. Cornwell, G.G.; Sletten, K.; Johansson, B.; Westermark, P. Evidence that the amyloid fibril protein in senile systemic amyloidosis is derived from normal prealbumin. Biochem. Biophys. Res. Commun. 1988, 154, 648-653.
17. Westermark, P.; Sletten, K.; Johansson, B.; Cornwell, G.G. Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proc. Natl. Acad. Sci. USA 1990, 87, 2843-2845.
18. Saraiva, M.J.; Costa, P.P.; Birken, S.; Goodman, D.S. Presence of an abnormal transthyretin (prealbumin) in Portuguese patients with familial amyloidotic polyneuropathy. Trans. Assoc. Am. Physicians 1983, 96, 261-270.
19. Hou, X.; Aguilar, M.-I.; Small, D.H. Transthyretin and familial amyloidotic polyneuropathy. Recent progress in understanding the molecular mechanism of neurodegeneration. FEBS J. 2007, 274, 1637-1650.
20. Jacobson, D.R.; McFarlin, D.E.; Kane, I.; Buxbaum, J.N. Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse amyloidosis with cardiac and neurologic involvement. Hum. Genet. 1992, 89, 353-356.
21. Saraiva, M.J. Transthyretin mutations in health and disease. Hum. Mutat. 1995, 5, 191-196.
22. Hammarström, P.; Jiang, X.; Hurshman, A.R.; Powers, E.T.; Kelly, J.W. Sequence-dependent denaturation energetics: A major determinant in amyloid disease diversity. Proc. Natl. Acad. Sci. USA 2002, 99, 16427-16432.
23. Lai, Z.; Colón, W.; Kelly, J.W. The acid-mediated denaturation pathway of transthyretin yields a conformational intermediate that can self-assemble into amyloid. Biochemistry 1996, 35, 6470-6482.
24. Quintas, A.; Saraiva, M.J.; Brito, R.M. The tetrameric protein transthyretin dissociates to a non-native monomer in solution. A novel model for amyloidogenesis. J. Biol. Chem. 1999, 274, 32943-32949.
25. Jiang, X.; Smith, C.S.; Petrassi, H.M.; Hammarström, P.; White, J.T.; Sacchettini, J.C.; Kelly, J.W. An engineered transthyretin monomer that is nonamyloidogenic, unless it is partially denatured. Biochemistry 2001, 40, 11442-11452.
26. Quintas, A.; Vaz, D.C.; Cardoso, I.; Saraiva, M.J.; Brito, R.M. Tetramer dissociation and monomer partial unfolding precedes protofibril formation in amyloidogenic transthyretin variants. J. Biol. Chem. 2001, 276, 27207-27213.
27. Ferrão-Gonzales, A.D.; Palmieri, L.; Valory, M.; Silva, J.L.; Lashuel, H.; Kelly, J.W.; Foguel, D. Hydration and packing are crucial to amyloidogenesis as revealed by pressure studies on transthyretin variants that either protect or worsen amyloid disease. J. Mol. Biol. 2003, 328, 963-974.
28. Sekijima, Y.; Wiseman, R.L.; Matteson, J.; Hammarström, P.; Miller, S.R.; Sawkar, A.R.; Balch, W.E.; Kelly, J.W. The biological and chemical basis for tissue-selective amyloid disease. Cell 2005, 121, 73-85.
29. Foss, T.R.; Wiseman, R.L.; Kelly, J.W. The pathway by which the tetrameric protein transthyretin dissociates. Biochemistry 2005, 44, 15525-15533.
30. Palaninathan, S.K.; Mohamedmohaideen, N.N.; Snee, W.C.; Kelly, J.W.; Sacchettini, J.C. Structural insight into pH-induced conformational changes within the native human transthyretin tetramer. J. Mol. Biol. 2008, 382, 1157-1167.
31. Ferrão-Gonzales, A.D.; Souto, S.O.; Silva, J.L.; Foguel, D. The preaggregated state of an amyloidogenic protein: Hydrostatic pressure converts native transthyretin into the amyloidogenic state. Proc. Natl. Acad. Sci. USA 2000, 97, 6445-6450.
32. Foguel, D. High pressure studies on transthyretin. Protein Pept. Lett. 2005, 12, 245-249.
33. Holmgren, G.; Ericzon, B.G.; Groth, C.G.; Steen, L.; Suhr, O.; Andersen, O.; Wallin, B.G.; Seymour, A.; Richardson, S.; Hawkins, P.N. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet 1993, 341, 1113-1116.
34. Herlenius, G.; Wilczek, H.E.; Larsson, M.; Ericzon, B.-G. Ten years of international experience with liver transplantation for familial amyloidotic polyneuropathy: Results from the familial amyloidotic polyneuropathy world transplant registry. Transplantation 2004, 77, 64-71.
35. Sekijima, Y.; Hammarström, P.; Matsumura, M.; Shimizu, Y.; Iwata, M.; Tokuda, T.; Ikeda, S.-I.; Kelly, J.W. Energetic characteristics of the new transthyretin variant A25T may explain its atypical central nervous system pathology. Lab. Invest. 2003, 83, 409-417.
36. Azevedo, E.P.C.; Pereira, H.M.; Garratt, R.C.; Kelly, J.W.; Foguel, D.; Palhano, F.L. Dissecting the structure, thermodynamic stability, and aggregation properties of the A25T transthyretin (A25T-TTR) variant involved in leptomeningeal amyloidosis: identifying protein partners that co-aggregate during A25T-TTR fibrillogenesis in cerebrospi. Biochemistry 2011, 50, 11070-11083.
37. Hammarström, P.; Sekijima, Y.; White, J.T.; Wiseman, R.L.; Lim, A.; Costello, C.E.; Altland, K.; Garzuly, F.; Budka, H.; Kelly, J.W. D18G transthyretin is monomeric, aggregation prone, and not detectable in plasma and cerebrospinal fluid: A prescription for central nervous system amyloidosis? Biochemistry 2003, 42, 6656-6663.
38. Bulawa, C.E.; Connelly, S.; Devit, M.; Wang, L.; Weigel, C.; Fleming, J.A.; Packman, J.; Powers, E.T.; Wiseman, R.L.; Foss, T.R.; et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc. Natl. Acad. Sci. USA 2012, 109, 9629-9634.
39. Johnson, S.M.; Connelly, S.; Fearns, C.; Powers, E.T.; Kelly, J.W. The transthyretin amyloidoses: From delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agency-approved drug. J. Mol. Biol. 2012, 421, 185-203.
40. Baures, P.W.; Oza, V.B.; Peterson, S.A.; Kelly, J.W. Synthesis and evaluation of inhibitors of transthyretin amyloid formation based on the non-steroidal anti-inflammatory drug, flufenamic acid. Bioorg. Med. Chem. 1999, 7, 1339-1347.
41. McCammon, M.G.; Scott, D.J.; Keetch, C.A.; Greene, L.H.; Purkey, H.E.; Petrassi, H.M.; Kelly, J.W.; Robinson, C.V. Screening transthyretin amyloid fibril inhibitors. Structure 2002, 10, 851-863.
42. Oza, V.B.; Smith, C.; Raman, P.; Koepf, E.K.; Lashuel, H.A.; Petrassi, H.M.; Chiang, K.P.; Powers, E.T.; Sachettinni, J.; Kelly, J.W. Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors. J. Med. Chem. 2002, 45, 321-332.
43. Lima, L.M.T.R.; Silva Vde, A.; Palmieri Lde, C.; Oliveira, M.C.B.R.; Foguel, D.; Polikarpov, I. Identification of a novel ligand binding motif in the transthyretin channel. Bioorg. Med. Chem. 2010, 18, 100-110.
44. Almeida, M.R.; Macedo, B.; Cardoso, I.; Alves, I.; Valencia, G.; Arsequell, G.; Planas, A.; Saraiva, M.J. Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. Biochem. J. 2004, 381, 351-356.
45. Johnson, S.M.; Connelly, S.; Wilson, I.A.; Kelly, J.W. Toward optimization of the linker substructure common to transthyretin amyloidogenesis inhibitors using biochemical and structural studies. J. Med. Chem. 2008, 51, 6348-6358.
46. Paladini, A.A.; Weber, G. Pressure-induced reversible dissociation of enolase. Biochemistry 1981, 20, 2587-2593.
47. Silva, J.L. Current topics new insights into the mechanisms of protein misfolding and aggregation in amyloidogenic diseases derived from pressure studies. Biochemistry 2004, 43, 11361-11370.
48. Lakowicz, J.R. Principles of Fluorescence Spectroscopy; Springer: New York, NY, USA, 2006; p. 980.
49. Royer, C.A. Probing protein folding and conformational transitions with fluorescence. Chem. Rev. 2006, 106, 1769-1784.
50. Cordeiro, Y.; Kraineva, J.; Suarez, M.C.; Tempesta, A.G.; Kelly, J.W.; Silva, J.L.; Winter, R.; Foguel, D. Fourier transform infrared spectroscopy provides a fingerprint for the tetramer and for the aggregates of transthyretin. Biophys. J. 2006, 91, 957-967.
51. Hurshman, A.R.; White, J.T.; Powers, E.T.; Kelly, J.W. Transthyretin aggregation under partially denaturing conditions is a downhill polymerization. Biochemistry 2004, 43, 7365-7381.
52. Taylor, B.M.; Sarver, R.W.; Fici, G.; Poorman, R.A.; Lutzke, B.S.; Molinari, A.; Kawabe, T.; Kappenman, K.; Buhl, A.E.; Epps, D.E. Spontaneous aggregation and cytotoxicity of the beta-amyloid Abeta1-40: A kinetic model. J. Protein Chem. 2003, 22, 31-40.
53. Sousa, M.M.; Cardoso, I.; Fernandes, R.; Guimarães, A.; Saraiva, M.J. Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: Evidence for toxicity of nonfibrillar aggregates. Am. J. Pathol. 2001, 159, 1993-2000.
54. Reixach, N.; Deechongkit, S.; Jiang, X.; Kelly, J.W.; Buxbaum, J.N. Tissue damage in the amyloidoses: Transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc. Natl. Acad. Sci. USA 2004, 101, 2817-2822.
55. Andersson, K.; Olofsson, A.; Nielsen, E.H.; Svehag, S.-E.; Lundgren, E. Only amyloidogenic intermediates of transthyretin induce apoptosis. Biochem. Biophys. Res. Commun. 2002, 294, 309-314.
56. Glenner, G.G.; Eanes, E.D.; Page, D.L. The relation of the properties of congo red-stained amyloid fibrils to the conformation. J. Histochem. Cytochem. 1972, 20, 821-826.
57. Klunk, W.E.; Jacob, R.F.; Mason, R.P. Quantifying amyloid by congo red spectral shift assay. Methods Enzymol. 1999, 309, 285-305.
58. Malmo, C.; Vilasi, S.; Iannuzzi, C.; Tacchi, S.; Cametti, C.; Irace, G.; Sirangelo, I. Tetracycline inhibits W7FW14F apomyoglobin fibril extension and keeps the amyloid protein in a pre-fibrillar, highly cytotoxic state. FASEB J. 2006, 20, 346-347.
59. Vilasi, S.; Sarcina, R.; Maritato, R.; De Simone, A.; Irace, G.; Sirangelo, I. Heparin induces harmless fibril formation in amyloidogenic W7FW14F apomyoglobin and amyloid aggregation in wild-type protein in vitro. PLoS One 2011, 6, e22076.
60. Bucciantini, M.; Giannoni, E.; Chiti, F.; Baroni, F.; Formigli, L.; Zurdo, J.; Taddei, N.; Ramponi, G.; Dobson, C.M.; Stefani, M. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 2002, 416, 507-511.
61. Gupta, S.; Chhibber, M.; Sinha, S.; Surolia, A. Design of mechanism-based inhibitors of transthyretin amyloidosis: studies with biphenyl ethers and new structural templates. J. Med. Chem. 2007, 50, 5589-5599.
62. Sirangelo, I.; Irace, G. Inhibition of aggregate formation as therapeutic target in protein misfolding diseases: Effect of tetracycline and trehalose. Expert Opin. Ther. Targets 2010, 14, 1311-1321.
63. Polikarpov, I.; Perles, L.A.; De Oliveira, R.T.; Oliva, G.; Castellano, E.E.; Garratt, R.C.; Craievich, A. Set-up and experimental parameters of the protein crystallography beamline at the Brazilian National Synchrotron Laboratory. J. Synchrotron Radiat. 1998, 5, 72-76.
64. Furnham, N.; Blundell, T.L.; DePristo, M.A.; Terwilliger, T.C. Is one solution good enough? Nat. Struct. Mol. Biol. 2006, 13, 184-185; discussion 185.
65. Hörnberg, A.; Eneqvist, T.; Olofsson, A.; Lundgren, E.; Sauer-Eriksson, A.E. A comparative analysis of 23 structures of the amyloidogenic protein transthyretin. J. Mol. Biol. 2000, 302, 649-669.
66. Potterton, L.; McNicholas, S.; Krissinel, E.; Gruber, J.; Cowtan, K.; Emsley, P.; Murshudov, G.N.; Cohen, S.; Perrakis, A.; Noble, M. Developments in the CCP4 molecular-graphics project. Acta Crystallogr. D Biol. Crystallogr. 2004, 60, 2288-2294.
67. Vagin, A.; Teplyakov, A. MOLREP: An automated program for molecular replacement. J. Appl. Crystallogr. 1997, 30, 1022-1025.
68. Murshudov, G.N.; Skubák, P.; Lebedev, A.A.; Pannu, N.S.; Steiner, R.A.; Nicholls, R.A.; Winn, M.D.; Long, F.; Vagin, A.A. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 2011, 67, 355-367.
69. Emsley, P.; Lohkamp, B.; Scott, W.G.; Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 2010, 66, 486-501.
70. Schüttelkopf, A.W.; van Aalten, D.M.F. PRODRG: A tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr. D Biol. Crystallogr. 2004, 60, 1355-1363.
71. Laskowski, R.A.; MacArthur, M.W.; Moss, D.S.; Thornton, J.M. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 1993, 26, 283-291.
72. Terwilliger, T.C.; Grosse-Kunstleve, R.W.; Afonine, P.V.; Moriarty, N.W.; Adams, P.D.; Read, R.J.; Zwart, P.H.; Hung, L.-W. Iterative-build OMIT maps: map improvement by iterative model building and refinement without model bias. Acta Crystallogr. D Biol. Crystallogr. 2008, 64, 515-524.