Improving binding specificity of pharmacological chaperones that target mutant superoxide dismutase-1 linked to familial amyotrophic lateral sclerosis using computational methods

Journal of Medicinal Chemistry

Volumn 53, Issue 7, 2010, Pages 2709-2718

  Nowak, Richard J ^d   Cuny, Gregory D ^a,b   Choi, Sungwoon ^a,b   Lansbury, Peter T ^a,c   Ray, Soumya S ^a,c  

^a The Harvard Center for Neurodegeneration & Repair   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AZAURACIL; CHAPERONE; COPPER ZINC SUPEROXIDE DISMUTASE; URACIL;

AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; BINDING SITE; CONTROLLED STUDY; DRUG BINDING; DRUG STRUCTURE; FAMILIAL DISEASE; HYDROGEN BOND; MATHEMATICAL MODEL; PLASMA; SITE DIRECTED MUTAGENESIS;

ABSORPTION; AMYOTROPHIC LATERAL SCLEROSIS; BINDING SITES; BUFFERS; COMPUTATIONAL BIOLOGY; DNA MUTATIONAL ANALYSIS; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; HUMANS; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MUTAGENESIS, SITE-DIRECTED; MUTANT PROTEINS; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; SUPEROXIDE DISMUTASE; URACIL;

EID: 77950562400     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm901062p     Document Type: Article

References (59)

1. Cohen, F. E.; Kelly, J. W. Therapeutic approaches to protein-misfolding diseases Nature 2003, 426, 905 - 909
2. Dobson, C. M. Protein aggregation and its consequences for human disease Protein Pept. Lett. 2006, 13, 219 - 227
3. Dobson, C. M. Principles of protein folding, misfolding and aggregation Semin. Cell Dev. Biol. 2004, 15, 3 - 16
4. Fink, A. L. Protein aggregation: folding aggregates, inclusion bodies and amyloid Folding Des. 1998, 3, R9 - 23
5. Fowler, D. M.; Kelly, J. W. Aggregating knowledge about prions and amyloid Cell 2009, 137, 20 - 22
6. Miroy, G. J.; Lai, Z.; Lashuel, H. A.; Peterson, S. A.; Strang, C. Inhibiting transthyretin amyloid fibril formation via protein stabilization Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 15051 - 15056
7. Baures, P. W.; Peterson, S. A.; Kelly, J. W. Discovering transthyretin amyloid fibril inhibitors by limited screening Bioorg. Med. Chem. 1998, 6, 1389 - 1401
8. Adamski-Werner, S. L.; Palaninathan, S. K.; Sacchettini, J. C.; Kelly, J. W. Diflunisal analogues stabilize the native state of transthyretin. Potent inhibition of amyloidogenesis J. Med. Chem. 2004, 47, 355 - 374
9. Sawkar, A. R.; Adamski-Werner, S. L.; Cheng, W. C.; Wong, C. H.; Beutler, E. Gaucher disease-associated glucocerebrosidases show mutation-dependent chemical chaperoning profiles Chem. Biol. 2005, 12, 1235 - 1244
10. Sawkar, A. R.; Schmitz, M.; Zimmer, K. P.; Reczek, D.; Edmunds, T. Chemical chaperones and permissive temperatures alter localization of Gaucher disease associated glucocerebrosidase variants ACS Chem. Biol. 2006, 1, 235 - 251
11. Arakawa, T.; Ejima, D.; Kita, Y.; Tsumoto, K. Small molecule pharmacological chaperones: From thermodynamic stabilization to pharmaceutical drugs Biochim. Biophys. Acta 2006, 1764, 1677 - 1687
12. Jia, L. Y.; Gong, B.; Pang, C. P.; Huang, Y.; Lam, D. S.; Wang, N.; Yam, G. H.-F. A natural osmolyte corrects the disease phenotype of mutant myocilin causing glaucoma. Invest. Ophthalmol. Visual Sci. 2009, DOI: 10.1167/iovs.08-3151.
13. Lee, D.; Santos, D.; Al-Rawi, H.; McNeill, A. M.; Rugg, E. L. The chemical chaperone trimethylamine N -oxide ameliorates the effects of mutant keratins in cultured cells Br. J. Dermatol. 2008, 159, 252 - 255
14. Mehta, A. D.; Seidler, N. W. Beta-alanine suppresses heat inactivation of lactate dehydrogenase J. Enzyme Inhib. Med. Chem. 2005, 20, 199 - 203
15. Kanki, K.; Kawamura, T.; Watanabe, Y. Control of ER stress by a chemical chaperone counteracts apoptotic signals in IFN-gamma-treated murine hepatocytes Apoptosis 2009, 14, 309 - 319
16. Park, J. Y.; Kim, G. H.; Kim, S. S.; Ko, J. M.; Lee, J. J. Effects of a chemical chaperone on genetic mutations in alpha-galactosidase A in Korean patients with Fabry disease Exp. Mol. Med. 2009, 41, 1 - 7
17. Sekijima, Y.; Dendle, M. A.; Kelly, J. W. Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis Amyloid 2006, 13, 236 - 249
18. Reixach, N.; Adamski-Werner, S. L.; Kelly, J. W.; Koziol, J.; Buxbaum, J. N. Cell based screening of inhibitors of transthyretin aggregation Biochem. Biophys. Res. Commun. 2006, 348, 889 - 897
19. Klabunde, T.; Petrassi, H. M.; Oza, V. B.; Raman, P.; Kelly, J. W. Rational design of potent human transthyretin amyloid disease inhibitors Nat. Struct. Biol. 2000, 7, 312 - 321 (Pubitemid 30194456)
20. Oza, V. B.; Petrassi, H. M.; Purkey, H. E.; Kelly, J. W. Synthesis and evaluation of anthranilic acid-based transthyretin amyloid fibril inhibitors Bioorg. Med. Chem. Lett. 1999, 9, 1 - 6
21. 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
22. Sawkar, A. R.; D'Haeze, W.; Kelly, J. W. Therapeutic strategies to ameliorate lysosomal storage disorders: a focus on Gaucher disease Cell. Mol. Life Sci. 2006, 63, 1179 - 1192
23. Sawkar, A. R.; Cheng, W. C.; Beutler, E.; Wong, C. H.; Balch, W. E. Chemical chaperones increase the cellular activity of N370S beta-glucosidase: a therapeutic strategy for Gaucher disease Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 15428 - 15433
24. Rosen, D. R.; Sapp, P.; O'Regan, J.; McKenna-Yasek, D.; Schlumpf, K. S. Genetic linkage analysis of familial amyotrophic lateral sclerosis using human chromosome 21 microsatellite DNA markers Am. J. Med. Genet. 1994, 51, 61 - 69
25. Radunovic, A.; Leigh, P. N. ALSODatabase: database of SOD1 (and other) gene mutations in ALS on the Internet. European FALS Group and ALSOD Consortium Amyotrophic Lateral Scler. Other Mot. Neuron Disord. 1999, 1, 45 - 49
26. Hayward, L. J.; Rodriguez, J. A.; Kim, J. W.; Tiwari, A.; Goto, J. J. Decreased metallation and activity in subsets of mutant superoxide dismutases associated with familial amyotrophic lateral sclerosis J. Biol. Chem. 2002, 277, 15923 - 15931
27. Hough, M. A.; Grossmann, J. G.; Antonyuk, S. V.; Strange, R. W.; Doucette, P. A. Dimer destabilization in superoxide dismutase may result in disease-causing properties: structures of motor neuron disease mutants Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5976 - 5981
28. Tiwari, A.; Hayward, L. J. Mutant SOD1 instability: implications for toxicity in amyotrophic lateral sclerosis Neurodegener. Dis. 2005, 2, 115 - 127
29. Rodriguez, J. A.; Shaw, B. F.; Durazo, A.; Sohn, S. H.; Doucette, P. A. Destabilization of apoprotein is insufficient to explain Cu,Zn-superoxide dismutase-linked ALS pathogenesis Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 10516 - 10521
30. Strange, R. W.; Antonyuk, S.; Hough, M. A.; Doucette, P. A.; Rodriguez, J. A. The structure of holo and metal-deficient wild-type human Cu, Zn superoxide dismutase and its relevance to familial amyotrophic lateral sclerosis J. Mol. Biol. 2003, 328, 877 - 891
31. Rodriguez, J. A.; Valentine, J. S.; Eggers, D. K.; Roe, J. A.; Tiwari, A. Familial amyotrophic lateral sclerosis-associated mutations decrease the thermal stability of distinctly metallated species of human copper/zinc superoxide dismutase J. Biol. Chem. 2002, 277, 15932 - 15937
32. Elam, J. S.; Malek, K.; Rodriguez, J. A.; Doucette, P. A.; Taylor, A. B. An alternative mechanism of bicarbonate-mediated peroxidation by copper-zinc superoxide dismutase: rates enhanced via proposed enzyme-associated peroxycarbonate intermediate J. Biol. Chem. 2003, 278, 21032 - 21039
33. Elam, J. S.; Taylor, A. B.; Strange, R.; Antonyuk, S.; Doucette, P. A. Amyloid-like filaments and water-filled nanotubes formed by SOD1 mutant proteins linked to familial ALS Nat. Struct. Biol. 2003, 10, 461 - 467
34. Antonyuk, S.; Elam, J. S.; Hough, M. A.; Strange, R. W.; Doucette, P. A. Structural consequences of the familial amyotrophic lateral sclerosis SOD1 mutant His46Arg Protein Sci. 2005, 14, 1201 - 1213
35. Tiwari, A.; Xu, Z.; Hayward, L. J. Aberrantly increased hydrophobicity shared by mutants of Cu,Zn-superoxide dismutase in familial amyotrophic lateral sclerosis J. Biol. Chem. 2005, 280, 29771 - 29779 (Pubitemid 41177054)
36. Cao, X.; Antonyuk, S. V.; Seetharaman, S. V.; Whitson, L. J.; Taylor, A. B. Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis J. Biol. Chem. 2008, 283, 16169 - 16177
37. Chattopadhyay, M.; Durazo, A.; Sohn, S. H.; Strong, C. D.; Gralla, E. B. Initiation and elongation in fibrillation of ALS-linked superoxide dismutase Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 18663 - 18668
38. Banci, L.; Bertini, I.; Boca, M.; Girotto, S.; Martinelli, M. SOD1 and amyotrophic lateral sclerosis: mutations and oligomerization PLoS One 2008, 3, e1677
39. Valentine, J. S. Do oxidatively modified proteins cause ALS? Free Radical Biol. Med. 2002, 33, 1314 - 1320
40. Strange, R. W.; Antonyuk, S. V.; Hough, M. A.; Doucette, P. A.; Valentine, J. S. Variable metallation of human superoxide dismutase: atomic resolution crystal structures of Cu-Zn, Zn-Zn and as-isolated wild-type enzymes J. Mol. Biol. 2006, 356, 1152 - 1162
41. Doucette, P. A.; Whitson, L. J.; Cao, X.; Schirf, V.; Demeler, B. Dissociation of human copper-zinc superoxide dismutase dimers using chaotrope and reductant. Insights into the molecular basis for dimer stability J. Biol. Chem. 2004, 279, 54558 - 54566
42. Goto, J. J.; Zhu, H.; Sanchez, R. J.; Nersissian, A.; Gralla, E. B. Loss of in vitro metal ion binding specificity in mutant copper-zinc superoxide dismutases associated with familial amyotrophic lateral sclerosis J. Biol. Chem. 2000, 275, 1007 - 1014
43. Lyons, T. J.; Nersissian, A.; Huang, H.; Yeom, H.; Nishida, C. R. The metal binding properties of the zinc site of yeast copper-zinc superoxide dismutase: implications for amyotrophic lateral sclerosis J. Biol. Inorg. Chem. 2000, 5, 189 - 203
44. Khare, S. D.; Dokholyan, N. V. Common dynamical signatures of familial amyotrophic lateral sclerosis-associated structurally diverse Cu, Zn superoxide dismutase mutants Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 3147 - 3152
45. Shaw, B. F.; Durazo, A.; Nersissian, A. M.; Whitelegge, J. P.; Faull, K. F. Local unfolding in a destabilized, pathogenic variant of superoxide dismutase 1 observed with H/D exchange and mass spectrometry J. Biol. Chem. 2006, 281, 18167 - 18176
46. Valentine, J. S.; Hart, P. J. Misfolded CuZnSOD and amyotrophic lateral sclerosis Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 3617 - 3622
47. Shaw, B. F.; Valentine, J. S. How do ALS-associated mutations in superoxide dismutase 1 promote aggregation of the protein? Trends Biochem. Sci. 2007, 32, 78 - 85
48. Banci, L.; Bertini, I.; D'Amelio, N.; Libralesso, E.; Turano, P. Metalation of the amyotrophic lateral sclerosis mutant glycine 37 to arginine superoxide dismutase (SOD1) apoprotein restores its structural and dynamical properties in solution to those of metalated wild-type SOD1 Biochemistry 2007, 46, 9953 - 9962
49. Ray, S. S.; Lansbury, P. T., Jr. A possible therapeutic target for Lou Gehrig's disease Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5701 - 5702
50. Ray, S. S.; Nowak, R. J.; Brown, R. H., Jr.; Lansbury, P. T., Jr. Small-molecule-mediated stabilization of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants against unfolding and aggregation Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 3639 - 3644
51. Grossman, I. ADME pharmacogenetics: current practices and future outlook Expert Opin. Drug Metab. Toxicol. 2009, 5, 449 - 462
52. Ray, S. S.; Nowak, R. J.; Strokovich, K.; Brown, R. H., Jr.; Walz, T. An intersubunit disulfide bond prevents in vitro aggregation of a superoxide dismutase-1 mutant linked to familial amytrophic lateral sclerosis Biochemistry 2004, 43, 4899 - 4905
53. Santoro, M. M.; Bolen, D. W. A test of the linear extrapolation of unfolding free energy changes over an extended denaturant concentration range Biochemistry 1992, 31, 4901 - 4907
54. 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
55. Johnson, S. M.; Connelly, S.; Wilson, I. A.; Kelly, J. W. Toward optimization of the second aryl substructure common to transthyretin amyloidogenesis inhibitors using biochemical and structural studies J. Med. Chem. 2009, 52, 1115 - 1125
56. Purkey, H. E.; Dorrell, M. I.; Kelly, J. W. Evaluating the binding selectivity of transthyretin amyloid fibril inhibitors in blood plasma Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 5566 - 5571
57. Wilcox, K. C.; Zhou, L.; Jordon, J. K.; Huang, Y.; Yu, Y. Modifications of superoxide dismutase (SOD1) in human erythrocytes: a possible role in amyotrophic lateral sclerosis J. Biol. Chem. 2009, 284, 13940 - 13947
58. Fabrini, R.; De Luca, A.; Stella, L.; Mei, G.; Orioni, B. Monomer-dimer equilibrium in glutathione transferases: a critical re-examination Biochemistry 2009, 48, 10473 - 10482
59. Islam, M. M.; Sohya, S.; Noguchi, K.; Kidokoro, S.; Yohda, M. Thermodynamic and structural analysis of highly stabilized BPTIs by single and double mutations Proteins 2009, 77, 962 - 970