Structure-activity relationships for a series of compounds that inhibit aggregation of the Alzheimer's peptide, Aβ42

Chemical Biology and Drug Design

Volumn 84, Issue 5, 2014, Pages 505-512

  McKoy, Angela F ^a   Chen, Jermont ^a   Schupbach, Trudi ^a   Hecht, Michael H ^a  

^a PRINCETON UNIVERSITY   (United States)

Author keywords

Amyloid beta aggregation inhibitors; Biologic screening; Chemical biology; Chemical structure; Drug discovery

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; D 744; D 830; N [2 (3,4 DICHLOROPHENYL)ETHYL] N METHYL 2 (1 PYRROLIDINYL)CYCLOHEXYLAMINE; OLIGOMER; PROTEIN INHIBITOR; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN; AMYLOID BETA-PROTEIN (1-42); MOLECULAR LIBRARY; PEPTIDE FRAGMENT;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DROSOPHILA MELANOGASTER; DRUG SCREENING; DRUG STRUCTURE; FEMALE; HIGH THROUGHPUT SCREENING; LOCOMOTION; LONGEVITY; NONHUMAN; PROTEIN AGGREGATION; RAT; STRUCTURE ACTIVITY RELATION; TRANSGENIC DROSOPHILA; AGING; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; GENETICS; HUMAN; MALE; MOLECULAR LIBRARY; PHARMACOLOGY; PROCEDURES; TOXICITY TESTING; TRANSGENIC ANIMAL;

AGING; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; ANIMALS, GENETICALLY MODIFIED; DROSOPHILA MELANOGASTER; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MALE; PEPTIDE FRAGMENTS; RATS; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; TOXICITY TESTS;

EID: 84908070530     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/cbdd.12341     Document Type: Article

References (44)

1. Sperling R.A., Jack C.R. Jr, Aisen P.S. (2011) Testing the right target and right drug at the right stage. Sci Transl Med;3:111cm33.
2. Clippingdale A., Wade J., Barrow C. (2001) The amyloid-beta peptide and its role in Alzheimer's disease. J Pept Sci;7:227-249.
3. Hardy J., Higgens G. (1992) Alzheimer's disease: the amyloid cascade hypothesis. Science;956:184-185.
4. Alexandrescu A. (2005) Amyloid accomplices and enforcers. Protein Sci;14:1-12.
5. Selkoe D.J., Shenk D. (2003) Alzheimer's disease: molecular understanding predicts amyloid based therapeutics. Annu Rev Pharmacol Toxicol;43:545-584.
6. Hardy J., Allsop D. (1991) Amyloid deposition as the central event in the etiology of Alzheimer's disease. Trends Pharmacol Sci;12:383-388.
7. Masters C., Simms G., Weiman N., Multhaup G., McDonald B., Beyreuther K. (1985) Amyloid plaque core protein in Alzheimer's disease and Down syndrome. PNAS;82:4245-4249.
8. Selkoe D. (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol Rev;81:741-766.
9. Walsh D.M., Hartley D.M. (1999) Amyloid beta protein fibrillogenesis structure and biological activity of proto-fibrillar intermediates. J Biol Chem;274:25945-25952.
10. Walsh D.M., Klyubin I., Fadeeva J.V., Cullen W.K., Anwyl R., Wolfe M.S., Rowan M.J., Selkoe D.J. (2002) Naturally secreted oligomers of amyloid- β protein potently inhibit hippocampal long-term potentiation in vivo. Nature;416:535-539.
11. Lesne S., Koh M.T., Kotilinek L., Kayed R., Glabe C.G., Yang A., Gallagher M., Ashe K.H. (2006) A specific amyloid-β protein assembly in the brain impairs memory. Nature;440:352-357.
12. Haass C., Selkoe D.J. (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β peptide. Nat Rev Mol Cell Biol;8:101-112.
13. Kayed R., Head E., Thompson J., McIntire T., Milton S., Cotman C., Glabe C. (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science;300:486-489.
14. Hefti F., Goure W.F., Jerecic J., Iverson K.S., Walike P.A., Krafft G.A. (2013) The case for soluble Aβ oligomers as a drug target in Alzheimer's disease. Trends Pharmacol Sci;34:261-266.
15. Necula M., Kayed R., Milton S., Glabe C. (2007) Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct. J Biol Chem;282:10311-10324.
16. Necula M., Breydo L., Milton S., Kayed R., van der Veer W., Glabe C. (2007) Methylene blue inhibits amyloid A-beta oligomerization by promoting fibrillization. Biochemistry;46:8850-8860.
17. Reinke A., Gestwicki J. (2007) Structure-activity relationships of amyloid beta aggregation inhibitors based on curcumin: influence of linker length and flexibility. Chem Biol Drug Des;70:206-215.
18. Wang H., Shorter S. (2008) Direct and selective elimination of specific prions and amyloid by 4,5-dianilinophthalimide analogs. PNAS;105:7159-7164.
19. Klafki H.W., Staufenbiel M., Kornhuber J., Wiltfang J. (2006) Therapeutic approaches to Alzheimer's disease. Brain;129:2840-2855.
20. Citron M. (2010) Alzheimer's disease: strategies for disease modification. Nat Rev Drug Discovery;9:387-398.
21. Porat Y., Abramowitz A., Gazit E. (2006) Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chem Biol Drug Des;67:27-37.
22. Hawkes C., Ng V., McLaurin J. (2009) Small molecule inhibitors of A-beta aggregation and neurotoxicity. Drug Dev Res;70:111-124.
23. Cheng P.N., Liu C., Zhao M., Eisenberg D., Nowick J.S. (2012) Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity. Nat Chem;4:927-933.
24. Kim W., Kim Y., Min J., Kim D., Chang Y., Hecht M. (2006) A high-throughput screen for compounds that inhibit aggregation of the Alzheimer's peptide. ACS Chem Biol;1:461-469.
25. Chen J., Armstrong A.H., Koehler A., Hecht M.H. (2010) Small molecule microarrays enable the discovery of compounds that bind the Alzheimer's Aβ peptide and reduce cytotoxicity. J Am Chem Soc;132:17015-17022.
26. Petkova A.T., Ishii Y., Leapman R., Delaglio F., Tycko R. (2002) A structural model for Alzheimer's beta-amyloid fibrils based on experimental constraints from solid state NMR. PNAS;26:16742-16747.
27. Petkova A.T., Yau W., Tycko R. (2006) Experimental constrains on quaternary structure in Alzheimer's beta-amyloid fibrils. Biochemistry;45:498-512.
28. Paravastua A.K., Leapmanb R.D., Yaua W.-M., Tycko R. (2008) Molecular structural basis for polymorphism in Alzheimer's β-amyloid fibrils. PNAS;105:18349-18354.
29. Fitzpatrick , et al. (2013) Atomic structure and hierarchical assembly of a cross-β amyloid fibril. PNAS;110:5468-5473.
30. Laganowsky A., Liu C., Sawaya M.R., Whitelegge J.P., Park J., Zhao M., Pensalfini A., Soriaga A.B., Landau M., Teng P.K., Cascio D., Glabe C., Eisenberg D. (2012) Atomic view of a toxic amyloid small oligomer. Science;335:1228-1231.
31. Jiang L., Liu C., Leibly C., Landau M., Zhao M., Hughes M.P., Eisenberg D.S. (2013) Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta. ELife;2:e00857.
32. McKoy A.F., Chen J., Schupbach T., Hecht M.H. (2012) A novel inhibitor of amyloid β(Aβ) peptide aggregation: from high throughput screening to efficacy in an animal model of Alzheimer's Disease. J Biol Chem;287:38992-39000.
33. Scherzer-Attali R., Pellarin R., Convertino M., Frydman-Marom A., Egoz-Matia N., Peled S., Levy-Sakin M., Shalev D., Caflisch A., Gazit E., Segal D. (2010) Complete phenotypic recovery of an Alzheimer's disease model by a Quinone-Tryptophan hybrid aggregation inhibitor. PLoS ONE;5:e11101.
34. Waldo G.S., Standish B.M. (1999) Rapid protein folding assay using green fluorescent Protein. Nat Biotechnol; 17:691-695.
35. Wurth C., Guimard N.K., Hecht M.H. (2002) Mutations that reduce aggregation of the Alzheimer's Aβ42 peptide: an unbiased search for the sequence determinants of Aβ amyloidogenesis. J Mol Biol;319:1279-1290.
36. Araman H., Resnati G., Metrangolo P. (2008) Halogen Bonding: Fundamentals and Applications. Berlin, Germany: Springer Publishing.
37. Zhu W., Wang Y., Yunxian L. (2010) Nonbonding interactions of organic halogens in biological systems: implications for drug discovery and biomolecular design. Phys Chem Chem Phys;12:4543-4551.
38. Walsh D.M., Selkoe D.J. (2007) A beta oligomers-a decade of discovery. J Neurochem;101:1172-1184.
39. McLean C.A., Cherny R.A. (1999) Soluble pool of a beta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol;46:860-866.
40. Walsh D.M., Selkoe D.J. (2004) Oligomers in the brain: the emerging role of protein aggregates in neurodegeneration. Protein Pept Lett;11:213-228.
41. Petkova A.T., Leapman R.D., Guo Z.H., Yau W.M., Mattson M.P., Tycko R. (2005) Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils. Science;307:262.
42. Mosmann T. (1983) Rapid colorometric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods;65:55-63.
43. Crowther D.C., Kinghorn K.J., Miranda E., Page R., Curry J.A., Duthie F., Gubb D.C., Lomas D.A. (2005) Intraneuronal amyloid beta non-amyloid aggregates and neurodegeneration a drosophila model of Alzheimer's disease. Neuroscience;132:123-135.
44. Pandey U., Nichols C. (2011) Human disease models in Drosophila Melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev;63:411-436.