Small molecules that target protein misfolding

Journal of Medicinal Chemistry

Volumn 55, Issue 24, 2012, Pages 10823-10843

  Gavrin, Lori Krim ^a   Denny, Rajiah Aldrin ^a   Saiah, Eddine ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2,4,6 TRIIODOPHENOL; 4 (3 DIMETHYLAMINOPROPYLAMINO) 2 (4 METHOXYSTYRYL)QUINAZOLINE; 4 PHENYLBUTYRIC ACID; AGENTS AFFECTING PROTEIN METABOLISM; ALPHA 1 ANTITRYPSIN; CONIVAPTAN; COPPER ZINC SUPEROXIDE DISMUTASE; DIFLUNISAL; EPRODISATE; ERYTHRITOL; GLUCOSE; GLYCEROL; LIXIVAPTAN; LYSOZYME; MOZAVAPTAN; MUTANT P53 DEPENDENT INDUCTION OF RAPID APOPTOSIS 3; P53 REACTIVATION AND INDUCTION OF MASSIVE APOPTOSIS 1; PREALBUMIN; PROTEIN P53; RELCOVAPTAN; RILUZOLE; SATAVAPTAN; SCH 529074; SERUM AMYLOID A; SH GROUP TARGETING COMPOUND THAT INDUCES MASSIVE APOPTOSIS 1; TAFAMIDIS; TOLVAPTAN; TREHALOSE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASOPRESSIN V2 RECEPTOR; VPA 895;

AMYLOIDOSIS; AMYOTROPHIC LATERAL SCLEROSIS; BINDING AFFINITY; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TARGETING; FAMILIAL AMYLOID POLYNEUROPATHY; GAIN OF FUNCTION MUTATION; HUMAN; KIDNEY AMYLOIDOSIS; LOSS OF FUNCTION MUTATION; NONHUMAN; PRION; PROTEIN AGGREGATION; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN DNA BINDING; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN MISFOLDING; PROTEIN STABILITY; PROTEIN STRUCTURE; PROTEIN TARGETING; REVIEW;

ALPHA 1-ANTITRYPSIN; AMYLOID; ANIMALS; HUMANS; MODELS, MOLECULAR; MURAMIDASE; MUTATION; NEURODEGENERATIVE DISEASES; PREALBUMIN; PRIONS; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN FOLDING; PROTEINS; PROTEOSTASIS DEFICIENCIES; RECEPTORS, VASOPRESSIN; SERUM AMYLOID A PROTEIN; SMALL MOLECULE LIBRARIES; SUPEROXIDE DISMUTASE; TUMOR SUPPRESSOR PROTEIN P53; UNFOLDED PROTEIN RESPONSE;

EID: 84871650725     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301182j     Document Type: Review

References (174)

1. Campioni, S.; Monsellier, E.; Chiti, F. Why Proteins Misfold. In Protein Misfolding Diseases: Current and Emerging Principles and Therapies; Ramirez-Alvarado, M., Kelly, J. W., Dobson, C. M., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, 2010; pp 3-20.
2. Herczenik, E.; Gebbink, M. F. Molecular and cellular aspects of protein misfolding and disease FASEB J. 2008, 22, 2115-2133 (Pubitemid 351948631)
3. Ségalat, L. Loss-of-function genetic diseases and the concept of pharmaceutical targets Orphanet J. Rare Dis. 2007, 2, 30-36
4. Ellis, R. J. Macromolecular crowding: an important but neglected aspect of the intracellular environment Curr. Opin. Struct. Biol. 2001, 1, 114-119 (Pubitemid 32155560)
5. Hartl, F. U.; Hayer-Hartl, M. Molecular chaperones in the cytosol: from nascent chain to folded protein Science 2002, 295, 1852-1858 (Pubitemid 34214115)
6. Mayer, M. P. Gymnastics of molecular chaperones Mol. Cell 2010, 39, 321-331
7. Sloan, L. A.; Fillmore, M. C.; Churcher, I. Small-molecule modulation of cellular chaperones to treat protein misfolding disorders Curr. Opin. Drug Discovery Dev. 2009, 5, 666-681
8. Pettit, R. S. Cystic fibrosis transmembrane conductance regulator-modifying medications: the future of cystic fibrosis treatment Ann. Pharmacother. 2012, 46, 1065-1075
9. Smid, B. E.; Aerts, J. M.; Boot, R. G.; Linthorst, G. E.; Hollak, C. E. Pharmacological small molecules for the treatment of lysosomal storage disorders Expert Opin. Invest. Drugs 2010, 19, 1367-1379
10. Himmelstein, D. S.; Ward, S. M.; Lancia, J. K.; Patterson, K. R.; Binder, L. I. Tau as a therapeutic target in neurodegenerative disease Pharmacol. Ther. 2012, 136, 8-22
11. Lendel, C.; Bertoncini, C. W.; Cremades, N.; Waudby, C. A.; Vendruscolo, M.; Dobson, C. M.; Schenk, D.; Christodoulou, J.; Toth, G. On the mechanism of nonspecific inhibitors of protein aggregation: dissecting the interactions of alpha-synuclein with Congo red and lacmoid Biochemistry 2009, 48, 8322-8334
12. Blake, C. C.; Geisow, M. J.; Oatley, S. J.; Rerat, B.; Rerat, C. Structure of prealbumin: secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 Å J. Mo.l Biol. 1978, 121, 339-356 (Pubitemid 8361803)
13. Monaco, H. L.; Rizzi, M.; Coda, A. Structure of a complex of two plasma proteins: transthyretin and retinol-binding protein Science 1995, 268, 1039-1041
14. Wojtczak, A.; Luft, J.; Cody, V. Mechanism of molecular recognition. Structural aspects of 3,3′-diiodo- l -thyronine binding to human serum transthyretin J. Biol. Chem. 1992, 267, 353-357
15. White, J. T.; Kelly, J. W. Support for the multigenic hypothesis of amyloidosis: the binding stoichiometry of retinol-binding protein, vitamin A, and thyroid hormone influences transthyretin amyloidogenicity in vitro Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 13019-13024 (Pubitemid 33051310)
16. Dobson, C. M. Protein folding and misfolding Nature 2003, 426, 884-890 (Pubitemid 38056880)
17. Selkoe, D. J. Folding proteins in fatal ways Nature 2003, 426, 900-904 (Pubitemid 38056883)
18. Westermark, P.; Bergstrom, J.; Solomon, A.; Murphy, C.; Sletten, K. Transthyretin-derived senile systemic amyloidosis: clinicopathologic and structural considerations Amyloid 2003, 10, 48-54 (Pubitemid 37372567)
19. Westermark, P.; Sletten, K.; Johansson, B.; Cornwell, G. G. Fibril in senile systemic amyloidosis is derived from normal transthyretin Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 2843-2845
20. Jiang, X.; Buxbaum, J. N.; Kelly, J. W. The V122I cardiomyopathy variant of transthyretin increases the velocity of rate-limiting tetramer dissociation, resulting in accelerated amyloidosis Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 14943-14948 (Pubitemid 34013949)
21. Jacobson, D. R.; Pastore, R. D.; Yaghoubian, R.; Kane, I.; Gallo, G.; Buck, F. S.; Buxbaum, J. N. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans N. Engl. J. Med. 1997, 336, 466-473 (Pubitemid 27074357)
22. Sasaki, H.; Yoshioka, N.; Takagi, Y. Structure of the chromosomal gene for human serum prealbumin Gene 1985, 37, 191-197 (Pubitemid 16253454)
23. Sekijima, Y.; Hammarstrom, P.; Matsumura, M.; Shimizu, Y.; Iwata, M.; Tokuda, T.; Ikeda, S.; 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 (Pubitemid 36351002)
24. Hammarstrom, 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 (Pubitemid 36666106)
25. Plante-Bordeneuve, V.; Said, G. Transthyretin related familial amyloid polyneuropathy Curr. Opin. Neurol. 2000, 13, 569-573
26. Gambetti, P.; Russo, C. Human brain amyloidoses Nephrol., Dial., Transplant. 1998, 13 (Suppl. 7) 33-40 (Pubitemid 28534771)
27. Plante-Bordeneuve, V.; Said, G. Familial amyloid polyneuropathy Lancet Neurol. 2011, 10, 1086-1097
28. Said, G.; Grippon, S.; Kirkpatrick, P. Tafamidis Nat. Rev. Drug Discovery 2012, 11, 185-186
29. Jacobson, D. R.; Pastore, R. D.; Yaghoubian, R.; Kane, I.; Gallo, G.; Buck, F. S.; Buxbaum, J. N. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans N. Engl. J. Med. 1997, 336, 466-473 (Pubitemid 27074357)
30. 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 (Pubitemid 38745754)
31. Johnson, S. M.; Wiseman, R. L.; Sekijima, Y.; Green, N. S.; Adamski-Werner, S. L.; Kelly, J. W. Native state kinetic stabilization as a strategy to ameliorate protein misfolding diseases: a focus on the transthyretin amyloidoses Acc. Chem. Res. 2005, 38, 911-921
32. 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
33. 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. U.S.A. 1996, 93, 15051-15056 (Pubitemid 27009550)
34. Wojtczak, A.; Cody, V.; Luft, J. R.; Pangborn, W. Structures of human transthyretin complexed with thyroxine at 2.0 angstroms resolution and 3′,5′-dinitro- N -acetyl- l -thyronine at 2.2 angstroms resolution Acta Crystallogr., Sect. D: Biol. Crystrallogr. 1996, 52, 758-765
35. Wiseman, R. L.; Johnson, S. M.; Kelker, M. S.; Foss, T.; Wilson, I. A.; Kelly, J. W. Kinetic stabilization of an oligomeric protein by a single ligand binding event J. Am. Chem. Soc. 2005, 127, 5540-5551 (Pubitemid 40569865)
36. Connelly, S.; Choi, S.; Johnson, S. M.; Kelly, J. W.; Wilson, I. A. Structure-based design of kinetic stabilizers that ameliorate the transthyretin amyloidoses Curr. Opin. Struct. Biol. 2010, 20, 54-62
37. Sekijima, Y.; Dendle, M. A.; Kelly, J. W. Orally administered diflunisal stabilizes transthyretin against dissociation required for amyloidogenesis Amyloid 2006, 13, 236-249 (Pubitemid 44764463)
38. 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 (Pubitemid 38858463)
39. Coelho, T.; Maia, L.; Martins da Silva, A.; Waddington Cruz, M.; Plante-Bordeneuve, V.; Lozeron, P. A comprehensive evaluation of the disease-modifying effects of tafamidis in patients with transthyretin type familial amyloid polyneuropathy Neurology 2011, 76 (Suppl. 4) A111
40. Razavi, H.; Palaninathan, S. K.; Powers, E. T.; Wiseman, R. L.; Purkey, H. E.; Mohamedmohaideen, N. N.; Deechongkit, S.; Chiang, K. P.; Dendle, M. T.; Sacchettini, J. C.; Kelly, J. W. Benzoxazoles as transthyretin amyloid fibril inhibitors: synthesis, valuation, and mechanism of action Angew. Chem., Int. Ed. 2003, 42, 2758-2761 (Pubitemid 36807218)
41. European Medicines Agency (EMA). European Public AssessmentReport. EMA Web site, (2011. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR- Product-Information/human/002294/WC500117862.pdf
42. Choi, S.; Connelly, S.; Reixach, N.; Wilson, I. A.; Kelly, J. W. Chemoselective small molecules that covalently modify one lysine in a non-enzyme protein in plasma Nat. Chem. Biol. 2010) 6, 133-139
43. Kolstoe, S. E.; Mangione, P. P.; Bellotti, V.; Taylor, G. W.; Tenent, G. A.; Deroo, S.; Morrison, A. J.; Cobb, A. J. A.; Coyne, A.; McCammon, M. G.; Warner, T. D.; Mitchell, J.; Gill, R.; Smith, M. D.; Ley, S. V.; Robinson, C. V.; Wood, S. P.; Pepys, M. B. Trapping of palindromic ligands within native transthyretin prevents amyloid formation Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 20483-20488
44. Green, N. S.; Palaninathan, S. K.; Sacchettini, J. C.; Kelly, J. W. Synthesis and characterization of potent bivalent amyloidosis inhibitors that bind prior to transthyretin tetramerization J. Am. Chem. Soc. 2003, 125, 13404-13414 (Pubitemid 37352125)
45. The PyMOL Molecular Graphics System, version 1.5.0.4; Schrödinger, LLC: New York.
46. Brown, C. J.; Lain, S.; Verma, C. S.; Fersht, A. R.; Lane, D. P. Awakening guardian angels: drugging the p53 pathway Nat. Rev. Cancer 2009, 12, 862-873
47. Olivier, M.; Hollstein, M.; Hainaut, P. TP53 mutations in human cancers: origins, consequences, and clinical use Cold Spring Harbor Perspect. Biol. 2010, 1:a001008
48. Cho, Y.; Gorina, S.; Jeffrey, P. D.; Pavletich, N. P. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations Science 1994, 265, 346-355 (Pubitemid 24259959)
49. Discovery Studio, version 3.1; Accelrys Software Inc.: San Diego, CA, 2010.
50. Bullock, A. N.; Henckel, J.; DeDecker, B. S.; Johnson, C. M.; Nikolova, P. V.; Proctor, M. R.; Lane, D. P.; Fersht, A. R. Thermodynamic stability of wild-type and mutant p53 core domain Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 14338-14342 (Pubitemid 28041374)
51. Rippin, T. M.; Bykov, V. J.; Freund, S. M.; Selivanova, G.; Wiman, K. G.; Fersht, A. R. Characterization of the p53-rescue drug CP-31398 in vitro and in living cells Oncogene 2002, 21, 2119-2129 (Pubitemid 34311366)
52. Friedler, A.; Hansson, L. O.; Veprintsev, D. B.; Freund, S. M.; Rippin, T. M.; Nikolova, P. V.; Proctor, M. R.; Rüdiger, S.; Fersht, A. R. A peptide that binds and stabilizes p53 core domain: chaperone strategy for rescue of oncogenic mutants Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 937-942 (Pubitemid 34106614)
53. Foster, B. A.; Coffey, H. A.; Morin, M. J.; Rastinejad, F. Pharmacological rescue of mutant p53 conformation and function Science 1999, 286, 2507-2510
54. Bykov, V. J.; Issaeva, N.; Shilov, A.; Hultcrantz, M.; Pugacheva, E.; Chumakov, P.; Wiman, K. G.; Selivanova, G. Restoration of the tumor suppressorfunction to mutant p53 by a low-molecular-weight compound Nat. Med. 2002, 8, 282-288 (Pubitemid 34250107)
55. Bykov, V. J.; Issaeva, N.; Zache, N.; Shilov, A.; Hultcrantz, M.; Bergman, J.; Selivanova, G.; Wiman, K. G. Reactivation of mutant p53 and induction of apoptosis in human tumor cells by maleimide analogs J. Biol. Chem. 2005, 280, 30384-30391 (Pubitemid 41216221)
56. Zache, N.; Lambert, J. M.; Rökaeus, N.; Shen, J.; Hainaut, P.; Bergman, J.; Wiman, K. G.; Bykov, V. J. Mutant p53 targeting by the low molecular weight compound STIMA-1 Mol. Oncol. 2008, 2, 70-80
57. Joerger, A. C.; Ang, H. C.; Fersht, A. R. Structural basis for understanding oncogenic p53 mutations and designing rescue drugs Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 15056-15061 (Pubitemid 44583163)
58. Boeckler, F. M.; Joerger, A. C.; Jaggi, G.; Rutherford, T. J.; Veprintsev, D. B.; Fersht, A. R. Targeted rescue of a destabilized mutant of p53 by an in silico screened drug Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 10360-10365
59. Basse, N.; Kaar, J. L.; Settanni, G.; Joerger, A. C.; Rutherford, T. J.; Fersht, A. R. Toward the rational design of p53-stabilizing drugs: probing the surface of the oncogenic Y220C mutant Chem. Biol. 2010, 17, 46-56
60. Demma, M.; Maxwell, E.; Ramos, R.; Liang, L.; Li, C.; Hesk, D.; Rossman, R.; Mallams, A.; Doll, R.; Liu, M.; Seidel-Dugan, C.; Bishop, W. R.; Dasmahapatra, B. SCH529074, a small molecule activator of mutant p53, which binds p53 DNA binding domain (DBD), restores growth suppressive function to mutant p53 and interrupts HDM2-mediated ubiquitination of wild type p53 J. Biol. Chem. 2010, 285, 10198-10212
61. Goodsell, D. S.; Olson, A. J. Structural symmetry and protein function Annu. Rev. Biophys. Biomol. Struct. 2000, 29, 105-153 (Pubitemid 30599590)
62. 2+-superoxide dismutases by differential scanning calorimetry and Raman spectroscopy Arch. Biochem. Biophys. 1985, 241, 243-251 (Pubitemid 15012031)
63. Maestro, version 9.3; Schrödinger, LLC: New York, NY, 2012.
64. Gurney, M. E.; Pu, H.; Chiu, A. Y.; Dal Canto, M. C.; Polchow, C. Y.; Alexander, D. D.; Caliendo, J.; Hentati, A.; Kwon, Y. W.; Deng, H. X. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation Science 1994, 264, 1772-1775 (Pubitemid 24227760)
65. Bruijn, L. I.; Cleveland, D. W. Mechanisms of selective motor neuron death in ALS: insights from transgenic mouse models of motor neuron disease Neuropathol. Appl. Neurobiol. 1996, 22, 373-387 (Pubitemid 26355740)
66. Wang, Q.; Johnson, J. L.; Agar, N. Y.; Agar, J. N. Protein aggregation and protein instability govern familial amyotrophic lateral sclerosis patient survival PLoS Biol. 2008, 6, 1508-1526
67. Rakhit, R.; Chakrabartty, A. Structure, folding, and misfolding of Cu,Zn superoxide dismutase in amyotrophic lateral sclerosis Biochim. Biophys. Acta 2006, 1762, 1025-1037 (Pubitemid 44781177)
68. Hayward, L. J.; Rodriguez, J. A.; Kim, J. W.; Tiwari, A.; Goto, J. J.; Cabelli, D. E.; Valentine, J. S.; Brown, R. H., Jr. Decreased metallation and activity in subsets of mutant superoxide dismutases associated with familial amyotrophic lateral sclerosis J. Biol. Chem. 2002, 277, 15923-15931 (Pubitemid 34967873)
69. Tiwari, A.; Hayward, L. J. Familial amyotrophic lateral sclerosis mutants of copper/zinc superoxide dismutase are susceptible to disulfide reduction J. Biol. Chem. 2003, 278, 5984-5992 (Pubitemid 36800848)
70. Hough, M. A.; Grossmann, J. G.; Antonyuk, A.; Strange, R. W.; Doucette, P. A.; Rodriguez, J. A.; Whitson, L. J.; Hart, P. J.; Hayward, L. J.; Valentine, J. S.; Hasnain, S. S. 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 (Pubitemid 38520513)
71. Furukawa, Y.; Torres, A. S.; O'Halloran, T. V. Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS EMBO J. 2004, 23, 2872-2881 (Pubitemid 39013559)
72. Shaw, B. F.; Lelie, H. L.; Durazo, A.; Nersissian., A. M.; Xu, G.; Chan, P. K.; Gralla, E. B.; Tiwari, A.; Hayward, L. J.; Borchelt, D. R.; Valentine, J. S.; Whitelegge, J. P. Detergent-insoluble aggregates associated with amyotrophic lateral sclerosis in transgenic mice contain primarily full-length, unmodified superoxide dismutase-1 J. Biol. Chem. 2008, 283, 8340-8350
73. Ray, S. S.; Nowak, R. J.; Brown, R. H.; 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 (Pubitemid 40354664)
74. Nowak, R. J.; Cuny, G. D.; Choi, S.; Lansbury, P. T.; Ray, S. S. Improving binding specificity of pharmacological chaperones that target mutant superoxide dismutase-1 linked to familial amyotrophic lateral sclerosis using computational methods J. Med. Chem. 2010, 53, 2709-2718
75. Benmohamed, R.; Arvanites, A. C.; Kim, J.; Ferrante, R. J.; Silverman, R. B.; Morimoto, R. I.; Kirsch, D. R. Identification of compounds protective against G93A-SOD1 toxicity for the treatment of amyotrophic lateral sclerosis Amyotrophic Lateral Scler. 2011, 2, 87-96
76. Chen, T.; Benmohamed, R.; Kim, J.; Smith, K.; Amante, D.; Morimoto, R. I.; Kirsch, D. R.; Ferrante, R. J.; Silverman, R. B. ADME-guided design and synthesis of aryloxanyl pyrazolone derivatives to block mutant superoxide dismutase 1 (SOD1) cytotoxicity and protein aggregation: potential application for the treatment of amyotrophic lateral sclerosis J. Med. Chem. 2012, 55, 515-527
77. Zhang, W.; Benmohamed, R.; Arvanites, A. C.; Morimoto, R. I.; Ferrante, R. J.; Kirsch, D. R.; Silverman, R. B. Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells Bioorg. Med. Chem. 2012, 20, 1029-1045
78. Auclair, J. R.; Boggio, K. J.; Petsko, G. A.; Ringe, D.; Agar, J. N. Strategies for stabilizing superoxide dismutase (SOD1), the protein destabilized in the most common form of familial amyotrophic lateral sclerosis Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 21394-21399
79. Fleming, A. On a remarkable bacteriolytic element found in tissues and secretions Proc. R. Soc. London, Ser. B 1922, 93, 306-317
80. Blake, C. C. F.; Koenig, D. F.; Mair, G. A.; North, A. C. T.; Phillips, D. C.; Sarma, V. R. Structure of hen egg-white lysozyme: a three dimensional Fourier synthesis at 2 angstrom resolution Nature 1965, 206, 757-761
81. Phillips, D. C. The three-dimensional structure of an enzyme molecule Sci. Am. 1966, 215, 78-90
82. Reitamo, S.; Klockars, M.; Adinolfi, M.; Osserman, E. F. Human lysozyme: origin and distribution in health and disease Ricerca Clin. Lab. 1978, 8, 211-231
83. Jolles, P.; Jolles, J. What's new in lysozyme research? Mol. Cell. Biochem. 1984, 63, 165-189
84. Pepys, M. B.; Hawkins, P. N.; Booth, D. R.; Vigushin, D. M.; Tennent, G. A.; Soutar, A. K.; Totty, N.; Nguyen, O.; Blake, C. C.; Teryy, C. J.; Feest, T. G.; Zalin, A. M.; Hsuan, J. J. Human lysozyme gene mutations cause hereditary systemic amyloidosis Nature 1993, 362, 553-557 (Pubitemid 23113032)
85. Pepys, M. B. Amyloidosis Annu. Rev. Med. 2006, 57, 223-241 (Pubitemid 43261989)
86. Swaminathan, R.; Ravi, V. K.; Kumar, S.; Kumar, M. V.; Chandra, N. Lysozyme: a model protein for amyloid research Adv. Protein. Chem. Struct. Biol. 2011, 84, 63-111
87. Harrison, R. F.; Hawkins, P. N.; Roche, W. R.; MacHahon, R. F.; Hubscher, S. G.; Buckels, J. A. Fragile liver and massive hepatic haemorrhage due to hereditary amyloidosis Gut 1996, 38, 151-152 (Pubitemid 26020941)
88. Canet, D.; Sunde, M.; Last, A. M.; Miranker, A.; Spencer, A.; Robinson, C. V.; Dobson, C. M. Mechanistic studies of the folding of human lysozyme and the origin of amyloidogenic behavior in its disease-related variants Biochemistry 1999, 38, 6419-6427
89. Hooke, S. D.; Radford, S. E.; Dobson, C. M. The refolding of human lysozyme: a comparison with the structurally homologous hen lysozyme Biochemistry 1994, 33, 5867-5876 (Pubitemid 24184591)
90. Takano, K.; Funahashi, J.; Yutani, K. The stability and folding process of amyloidogenic mutant human lysozymes Eur. J. Biochem. 2001, 268, 155-159 (Pubitemid 32052259)
91. Wain, R.; Smith, L. J.; Dobson, C. M. Oxidative refolding of amyloidogenic variants of human lysozyme J. Mol. Biol. 2005, 351, 662-671 (Pubitemid 41021948)
92. Dumoulin, M. In Familial Amyloidosis Caused by Lysozyme in Protein Misfolding Diseases: Current and Emerging Principles and Therapies; Ramirez-Alvarado, M.; Kelly, J. W.; Dobson, C. M., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, 2010; pp 867-885.
93. Liu, H.-L.; Wu, Y.-C.; Zhao, J.-H.; Liu, Y.-F.; Huang, C.-H.; Fang, H.-W.; Ho, Y. Insights into the conformational changes of several human lysozyme variants associated with hereditary systemic amyloidosis Biotechnol. Prog. 2007, 23, 246-254 (Pubitemid 46293511)
94. Esposito, G.; Garcia, J.; Mangione, P.; Giorgetti, S.; Corazza, A.; Viglino, P.; Chiti, F.; Andreola, A.; Dumy, P.; Booth, D. Structural and folding dynamics properties of T70M variant of human lysozyme J. Biol. Chem. 2003, 278, 25910-25918 (Pubitemid 36835353)
95. Johnson, R. J.; Christodoulou, J.; Dumoulin, M.; Caddy, G. L.; Alcocer, M. J.; Murtagh, G. J.; Kumita, J. R.; Larsson, G.; Robinson, C. V.; Archer, D. B. Rationalizing lysozyme amyloidosis: insights from the structure and solution dynamics of T70N lysozyme J. Mol. Biol. 2005, 352, 823-836 (Pubitemid 41267071)
96. Booth, D. R; Sunde, M.; Bellotti, V.; Robinson, C. V.; Hutchinson, W. L.; Fraser, P. E.; Hawkins, P. N.; Dobson, C. M.; Radford, S. E.; Blake, C. C.; Pepys, M. B. Instability, unfolding, and aggregation of human lysozyme variants underlying amyloid fibrillogenesis Nature 1997, 385, 787-793 (Pubitemid 27106061)
97. Canet, D.; Last, A. M.; Tito, P.; Sunde, M.; Spencer, A.; Archer, D. B.; Redfield, C.; Robinson, C. V.; Dobson, C. M. Local cooperativity in the unfolding of an amyloidogenic variant of human lysozyme Nat. Struct. Biol. 2002, 9, 308-315 (Pubitemid 34289905)
98. Dumoulin, M.; Johnson, J. R. K.; Bellotti, V.; Dobson, C. M. In Protein Misfolding, Aggregation, and Conformational Diseases; Sipe, J. D., Ed.; VCH Verlag: Weinheim, Germany, 2007; Vol. II, pp 635-656.
99. Gazova, Z.; Bellova, A.; Daxnerova, Z.; Imrich, J.; Kristian, P.; Tomascikova, J.; Bagelova, J.; Fedunova, D.; Antalik, M. Acridine derivatives inhibit lysozyme aggregation Eur. Biophys. J. 2008, 37, 1261-1270
100. Antosova, A.; Chelli, B.; Bystrenova, E.; Siposova, K.; Valle, F.; Imrich, J.; Vilkova, M.; Kristian, P.; Biscarini, F.; Gazova, Z. Structure-activity relationship of acridine derivatives to amyloid aggregation of lysozyme Biochim. Biophys. Acta 2011, 1810, 465-474
101. May, B. C. H.; Fafarman, A. T.; Hong, S. B.; Roger, M.; Deady, L. W.; Prusiner, S. B.; Cohen, F. E. Potent inhibition of scrapie prion replication in cultured cells by bis-acridines Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 3416-3421 (Pubitemid 36356598)
102. Chan, P.-H.; Pardon, E.; Menzer, L.; De Genst, E.; Kumita, J. R.; Christodoulou, J.; Saerens, D.; Brans, A.; Bouillenne, F.; Archer, D. B.; Robinson, C. V.; Muyldermans, S.; Matagne, A.; Redfield, C.; Wyns, L.; Dobson, C. M.; Dumoulin, M. Engineering a camelid antibody fragment that binds to the active site of human lysozyme and inhibits its conversion into amyloid fibrils Biochemistry 2008, 47, 11041-11054
103. Harmsen, M. M.; De Haard, H. J. Properties, production, and applications of camelid single-domain antibody fragments Appl. Microbiol. Biotechnol. 2007, 77, 13-22 (Pubitemid 47573319)
104. Manley, P. N.; Ancsin, J. B.; Kisilevsky, R. Rapid recycling of cholesterol: the joint biologic role of C-reactive protein and serum amyloid A Med. Hypotheses 2006, 66, 784-792 (Pubitemid 43181624)
105. Yamada, T. Serum amyloid A (SAA): a concise review of biology, assay methods and clinical usefulness Clin. Chem. Lab. Med. 1999, 37, 381-388 (Pubitemid 29218956)
106. Tam, S. P.; Flexman, A.; Hulme, J.; Kisilevsky, R. Promoting export of macrophage cholesterol: the physiological role of a major acute-phase protein, serum amyloid A J. Lipid Res. 2002, 43, 1410-1420
107. Gabay, C.; Kushner, I. Acute-phase proteins and other systemic responses to inflammation N. Engl. J. Med. 1999, 340, 448-454 (Pubitemid 29084777)
108. Ajiro, J.; Narita, I.; Sato, F.; Saga, D.; Hasegawa, H.; Kuroda, T.; Nakano, M.; Gejyo, F. SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis Mod. Rheumatol. 2006, 16, 294-299 (Pubitemid 44575255)
109. Maury, C. P. J.; Aittoniemi, J.; Tiitinen, S.; Laiho, K.; Kaarela, K.; Hurme, M. Variant mannose-binding factor 2 genotype is a risk factor for reactive systemic amyloidosis in rheumatoid arthritis J. Intern. Med. 2007, 262, 466-469 (Pubitemid 47404366)
110. Hasegawa, H.; Nishi, S. I.; Ito, S.; Saeki, T.; Kuroda, T.; Kimura, H.; Watababe, T.; Nakano, M.; Gejyo, F.; Arakawa, M. High prevalence of serum apolipoprotein E4 isoprotein in rheumatoid arthritis patients with amyloidosis Arthritis Rheum. 1996, 39, 1728-1732 (Pubitemid 26331027)
111. Nakamura, T. Amyloid A amyloidosis secondary to rheumatoid arthritis: pathophysiology and treatments Clin. Exp. Rheumatol. 2011, 29, 850-857
112. Gertz, M. A.; Kyle, R. A. Secondary systemic amyloidosis: response and survival in 64 patients Medicine 1991, 70, 246-256
113. Obici, L.; Raimondi, S.; Lavatelli, F.; Bellotti, V.; Merlini, G. Susceptibility to AA amyloidosis in rheumatic diseases: a critical overview Arthritis Rheum. 2009, 61, 1435-1440
114. Wang, Y.; Srinivasan, S.; Ye, Z.; Aguilera, J. J.; Lopez, M. M.; Colon, W. Serum amyloid A 2.2 refolds into a octomeric oligomer that slowly converts to a more stable hexamer Biochem. Biophys. Res. Commun. 2011, 407, 725-729
115. Gillmore, J. D.; Lovat, L. B.; Persey, M. R.; Pepys, M. B.; Hawkins, P. N. Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein Lancet 2001, 358, 24-29 (Pubitemid 32709735)
116. Lachmann, H. J.; Goodman, J. J.; Gilbertson, J. A.; Gallimore, J. R.; Sabin, C. A.; Gillmore, J. D.; Hawkins, P. N. Natural history and outcome in systemic AA amyloidosis N. Engl. J. Med. 2007, 356, 2361-2371 (Pubitemid 46883770)
117. Pettersson, T.; Konttinen, Y. T.; Maury, C. P. J. Treatment strategies for amyloid A amyloidosis Expert Opin. Pharmacother. 2008, 9, 2117-2128
118. Dember, L. M.; Hawkins, P. N.; Hazenberg, B. P. C.; Gorevic, P. D.; Merlini, G.; Butrimiene, I.; Livneh, A.; Lesnyak, O.; Puechal, X; Lachmann, J. J.; Obici, L.; Balshaw, R.; Garceau, D.; Hauck, W.; Skinner, M. Eprodisate for the treatment of renal disease in AA amyloidosis N. Engl. J. Med. 2007, 356, 2349-2360 (Pubitemid 46883769)
119. International Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of the Efficacy and Safety of KIACTA in Preventing Renal Function Decline in Patients With AA Amyloidosis (Clinical Trials.gov Identifier: NCT01215747). http://clinicaltrials.gov/.
120. Loyd, S.; Mead, S.; Collinge, J. Genetics of Prion Disease. In Prion Proteins; Tatzelt, J., Ed.; Springer: Berlin, 2011, 305; pp 1-23.
121. Diaz-Espinoza, R.; Soto, C. Generation of prions in vitro and the protein-only hypothesis Prion 2010, 4, 1-7
122. Moreno-Gonzalez, I.; Soto, C. Misfolded protein aggregates: mechanisms, structures and potential for disease transmission Semin.Cell Dev. Biol. 2011, 5, 482-487
123. Weissmann, C.; Aguzzi, A. Approaches to therapy of prion diseases Annu. Rev. Med. 2005, 56, 321-344 (Pubitemid 40299786)
124. Tatzelt, J.; Prusiner, S. B.; Welch, W. J. Chemical chaperones interfere with the formation of scrapie prion protein EMBO J. 1996, 15, 6363-6373 (Pubitemid 26413769)
125. Caspi, S.; Halimi, M.; Yanai, A.; Sasson, S. B.; Taraboulos, A.; Gabizon, R. The anti-prion activity of Congo red. Putative mechanism J. Biol. Chem. 1998, 273, 3484-3489 (Pubitemid 28109769)
126. Perrier, V.; Wallace, A. C.; Kaneko, K.; Safar, J.; Prusiner, S. B.; Cohen, F. E. Mimicking dominant negative inhibition of prion replication through structure-based drug design Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 6073-6078 (Pubitemid 30367525)
127. Kaneko, K.; Zulianello, L.; Scott, M.; Cooper, C. M.; Wallace, A. C.; James, T. L.; Cohen, F. E.; Prusiner, S. B. Evidence for protein X binding to a discontinuous epitope on the cellular prion protein during scrapie prion propagation Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 10069-10074
128. Reddy, T. R.; Mutter, R.; Heal, W.; Guo, K.; Gillet, V. J.; Pratt, S.; Chen, B. Library design, synthesis, and screening: pyridine dicarbonitriles as potential prion disease therapeutics J. Med. Chem. 2006, 49, 607-615 (Pubitemid 43157491)
129. Guo, K; Mutter, R; Heal, W; Reddy, T. R.; Cope, H; Pratt, S; Thompson, M. J.; Chen, B. Synthesis and evaluation of a focused library of pyridine dicarbonitriles against prion disease Eur. J. Med. Chem. 2008, 43, 93-106
130. Bolognesi, M. L.; Ai Tran, H. N.; Staderini, M.; Monaco, A.; López-Cobeñas, A.; Bongarzone, S.; Biarnés, X.; López-Alvarado, P.; Cabezas, N.; Caramelli, M.; Carloni, P.; Menéndez, J. C.; Legname, G. Discovery of a class of diketopiperazines as antiprion compounds ChemMedChem 2010, 5, 1324-1334
131. van den Ouweland, A. M.; Knoop, M. T.; Knoers, V. V.; Markslag, P. W.; Rocchi, M.; Warren, S. T.; Ropers, H. H.; Fahrenholz, F.; Monnens, L. A.; van Oost, B. A. Colocalization of the gene for nephrogenic diabetes insipidus (NDI) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region Genomics 1992, 13, 1350-1352
132. Bichet, D. G. Nephrogenic diabetes insipidus Am. J. Med. 1998, 105, 431-442
133. Fujiwara, T. M.; Bichet, D. G. Molecular biology of hereditary diabetes insipidus J. Am. Soc. Nephrol. 2005, 16, 2836-2846 (Pubitemid 44743480)
134. Robben, J. H.; Knoers, N. V.; Deen, P. M. Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus Am. J. Physiol.: Renal Physiol. 2006, 291, F257-F270
135. McKinley, M. J.; Johnson, A. K. The physiological regulation of thirst and fluid intake News Physiol. Sci. 2004, 19, 1-6
136. Henderson, R.; Baldwin, J. M.; Ceska, T. A.; Zemlin, F.; Beckmann, E.; Downing, K. H. Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy Mol. Biol. 1990, 213, 899-903
137. Czaplewski, C.; Kazmierkiewicx, R.; Ciarkowski, J. Molecular modeling of the human vasopressin V2 receptor/agonist complex J. Comput.-Aided Mol. Des. 1998, 12, 275-287 (Pubitemid 128510956)
138. Czaplewski, C.; Kazmierkiewicx, R.; Ciarkowski, J. Molecular modelling of the vasopressin V2 receptor/antagonist interactions Acta Biochem. Pol. 1998, 45, 19-26 (Pubitemid 128646338)
139. Bichet, D. Vasopressin receptor mutations in nephrogenic diabetes insipidus Semin. Nephrol. 2008, 28, 245-251 (Pubitemid 351756520)
140. Conn, P.; Ulloa-Aguirre, A.; Ito, J.; Janovick, J. G protein-coupled receptor trafficking in health and disease: lessons learned to prepare for therapeutic mutant rescue in vivo Pharmacol. Rev. 2007, 59, 225-250 (Pubitemid 47481435)
141. Morello, J.; Salahpour, A.; Petaja-Repo, U.; Laperriere, A.; Lonergan, M.; Arthus, M.; Nabi, I. R.; Bichet, D.; Bouvier, M. Association of calnexin with wild type and mutant AVPR2 that cause nephrogenic diabetes insipidus Biochemistry 2001, 40, 6766-6775 (Pubitemid 32538222)
142. Rosenthal, W. P.; Seibold, A.; Antaramian, A.; Longergan, M.; Arthus, M.; Hendy, G.; Birnbaumer, M.; Bichet, D. Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus Nature 1992, 359, 233-235
143. Reeves, W.; Andreoli, T. Nephrogenic Diabetes Insipidus. In The Metabolic Basis of Inherited Disease; Scriver, S.; Beaudet, A.; Sly, W.; Valle, D.; McGraw-Hill: New York, 1989; pp 1985-2001.
144. Spanakis, E.; Milord, E.; Gragnoli, C. AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance J. Cell. Physiol. 2008, 217, 605-617
145. Morello, J.; Salahpour, A.; Laperriere, A.; Bernier, V.; Arthus, M.; Lonergan, M.; Petaja-Repo, U.; Angers, S.; Morin, D.; Bichet, D.; Bouvier, M. Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants J. Clin. Invest. 2000, 105, 887-895 (Pubitemid 30203061)
146. Bernier, V.; Bichet, D.; Bouvier, M. Pharmacological chaperone action on G-protein coupled receptors Curr. Opin. Pharmacol. 2004, 4, 528-533 (Pubitemid 40533016)
147. Bernier, V.; Lagace, M.; Lonergan, M.; Arthus, M.; Bichet, D.; Bouvier, M. Pharmacological chaperone action on G-protien-coupled recpetors Mol. Endocirnol. 2004, 18, 2074-2084
148. Bernier, V.; Morello, J.; Zarruk, A.; Debrand, N.; Salahpour, A.; Lonergan, M.; Arthus, M.; Laperriere, A.; Brouard, R.; Bouvier, M.; Bichet, D. Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus J. Am. Soc. Nephrol. 2006, 17, 232-243
149. Cheong, H.; Cho, H.; Park, H.; Ha, I. S.; Choi, Y. Molecular genetic study of congenital nephrogenic diabetes insipidus and rescue of mutant vasopressin V2 receptor by chemical chaperones Nephrology 2007, 12, 113-117 (Pubitemid 46426850)
150. Robben, J.; Sze, M.; Knoers, N.; Deen, P. Rescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism Mol. Biol. Cell 2006, 17, 379-386 (Pubitemid 43049490)
151. Wuller, S.; Wiesner, B.; Loffler, A.; Furkert, J.; Krause, G.; Hermosilla, R.; Schaefer, M.; Schulein, R.; Rosenthal, W.; Oksche, A. Pharmacochaperones post-translationally enhance cell surface expression by increasing conformational stability of wild-type and mutant vasopressin V2 receptors J. Biol. Chem. 2004, 279, 47254-47263 (Pubitemid 39518382)
152. Oueslati, M.; Hermosilla, R.; Schonenberger, E.; Oorschot, V.; Beyermann, M.; Wiesner, B.; Schmidt, A.; Klumperman, J.; Rosenthal, W.; Schulein, R. Rescue of a nephrogenic diabetes insipidus-causing vasopressin V2 receptor mutant by cell-penetrating peptides J. Biol. Chem. 2007, 282, 20676-20685 (Pubitemid 47100031)
153. Valenzano, K. J.; Benjamin, E. R.; Rene, P.; Bouvier, M. Pharmacological Chaperones: Potential for the Treatment of Hereditary Diseases Caused by Mutations in G Protein-Coupled Receptors. In GPCR Molecular Pharmacology and Drug Targeting: Shifting Paradigms and New Direction; Gilchrist, A., Ed.; John Wiley & Sons, Inc.: Hoboken, NJ, 2010
154. Robben, J.; Deen, P. Pharmacological chaperones in nephrogenic diabetes insipidus BioDrugs 2007, 21, 157-166
155. Stockley, R. A. Emerging drugs for alpha-1-antitrypsin deficiency Expert Opin. Emerging Drugs 2010, 15, 685-694
156. Perlmutter, D. H. Liver injury in alpha-1-antitrypsin deficiency: an aggregated protein induces mitochondrial injury J. Clin. Invest. 2002, 110, 1579-1583 (Pubitemid 35424232)
157. Greene, C. M.; McElvaney, N. G. Protein misfolding and obstructive lung disease Proc. Am. Thorac. Soc. 2010, 7, 346-355
158. Dafforn, T. R.; Mahadeva, R.; Elliott, P. R.; Sivasothy, P.; Lomas, D. A. A kinetic mechanism for the polymerisation of alpha-1-antitrypsin J. Biol. Chem. 1999, 274, 9548-9555
159. Purkayastha, P.; Klemke, J. W.; Lavender, S.; Oyola, R.; Cooperman, B. S.; Gai, F. alpha-1-Antitrypsin polymerisation: a fluorescence correlation spectroscopic study Biochemistry 2005, 44, 2642-2649 (Pubitemid 40279568)
160. Huntington, J. A.; Read, R. J.; Carrell, R. W. Structure of a serpin-protease complex shows inhibition by deformation Nature 2000, 407, 923-926
161. Molecular Operating Environment (MOE), version 2011.10; Chemical Computing Group Inc. (1010 Sherbooke St. West, Suite No. 910, Montreal, Quebec, Canada, H3A 2R7), 2011.
162. Stoller, J. K.; Aboussouan, L. S. alpha-1-Antitrypsin deficiency Lancet 2005, 365, 2225-2236
163. http://clinicaltrials.gov/ct2/show/NCT00670007?term=alpha-1- antitrypsin&phase=3&rank=2.
164. Bathurst, I. C.; Travis, J.; George, P. M.; Carrell, R. W. Structural and functional characterization of the abnormal Z alpha-1-antitrypsin isolated from human liver FEBS Lett. 1984, 177, 179-183 (Pubitemid 15213319)
165. Ogushi, F.; Fells, G. A.; Hubbard, R. C.; Straus, S. D.; Crystal, R. G. Z-Type alpha-1-antitrypsin is less competent than M1-type alpha-1-antitrypsin as an inhibitor of neutrophil elastase J. Clin. Invest. 1987, 80, 1366-1374 (Pubitemid 18027779)
166. Burrows, J. A.; Willis, L. K.; Perlmutter, D. H. Chemical chaperones mediate increased secretion of mutant alpha-1-antitrypsin Z: a potential pharmacological strategy for prevention of liver injury and emphysema in alpha-1-antitrypsin deficiency Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 1796-1801 (Pubitemid 30118522)
167. Sharpe, L. K.; Mallya, M.; Kinghorn, K. J.; Wang, Z.; Crowther, D. C.; Huntington, J. A.; Belorgey, D.; Lomas, D. A. Sugar and alcohol molecules provide a therapeutic strategy for the serpinopathies that cause dementia and cirrhosis FEBS J. 2006, 273, 2540-2552 (Pubitemid 43736665)
168. Zhou, A.; Stein, P. E.; Huntington, J. A.; Carrell, R. W. Serpin polymerisation is prevented by a hydrogen-bond network which is centered on His 334 and stabilised by glycerol J. Biol. Chem. 2003, 278, 15116-15122 (Pubitemid 36805596)
169. Teckman, J. H. Lack of effect of oral 4-phenylbutyrate on serum alpha-1-antitrypsin in patients with alpha-1-antitrypsin deficiency: a preliminary study J. Pediatr. Gastroenterol. Nutr. 2004, 1 (39) 34-37
170. Mallya, M.; Phillips, R. L.; Saldanha, S. A.; Gooptu, B.; Brown, S. C. L.; Termine, D. J.; Shirvani, A. M.; Wu, Y.; Sifers, R. N.; Abagyan, R.; Lomas, D. A. Small molecules block the polymerization of Z alpha-1-antitrypsin and increase the clearance of intracellular aggreagates J. Med. Chem. 2007, 50, 5357-5363 (Pubitemid 350057847)
171. Lee, C.; Maeng, J. S.; Kocher, J. P.; Lee, B.; Yu, M. H. Cavities of alpha-1-antitrypsin that play structural and functional roles Protein Sci. 2001, 10, 1446-1453 (Pubitemid 32568111)
172. Parfrey, H; Mahadeva, R.; Ravenhill, N.; Zhou, A.; Dafforn, T. R. Targeting a surface cavity of alpha-1-antitrypsin to prevent conformational disease J. Biol. Chem. 2003, 278, 33060-33066 (Pubitemid 37055752)
173. Chang, Y.-P.; Mahadeva, R.; Chang, W.-S. W.; Lin, S.-C.; Chu, Y.-H. Small molecule peptides inhibit Z alpha1-antitrypsin polymerization J. Cell. Mol. Med. 2009, 13, 2304-2316
174. Schulze, A. J.; Baumann, U.; Knof, S.; Jaeger, E.; Huber, R.; Laurell, C. B. Structural transition of alpha1-antitrypsin by a peptide sequentially similar to beta-strand s4A Eur. J. Biochem. 1990, 194, 51-56