Amyloid β-Protein Assembly: The Effect of Molecular Tweezers CLR01 and CLR03

Journal of Physical Chemistry B

Volumn 119, Issue 14, 2015, Pages 4831-4841

  Zheng, Xueyun ^a   Liu, Deyu ^a   Klärner, Frank Gerrit ^b   Schrader, Thomas ^b   Bitan, Gal ^c   Bowers, Michael T ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF DUISBURG ESSEN   (Germany)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIMERS; GLYCOPROTEINS; ION MOBILITY SPECTROMETERS; MASS SPECTROMETRY; MOLECULES; NEURODEGENERATIVE DISEASES; OLIGOMERIZATION; OLIGOMERS; SELF ASSEMBLY; SPECTROMETRY;

ALZHEIMER'S DISEASE; DIFFERENT EFFECTS; ION MOBILITY SPECTROMETRY; MOLECULAR TWEEZERS; NEGATIVE CONTROL; PROTEIN ASSEMBLY; SMALL MOLECULE INHIBITOR; SMALL MOLECULES;

PROTEINS;

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA-PROTEIN (1-42); BRIDGED COMPOUND; CLR01 COMPOUND; CLR03 COMPOUND; ORGANOPHOSPHATE; ORGANOPHOSPHORUS COMPOUND; PEPTIDE FRAGMENT;

CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; METABOLISM; PROTEIN MULTIMERIZATION; PROTEIN SECONDARY STRUCTURE;

AMYLOID BETA-PEPTIDES; BRIDGED COMPOUNDS; MODELS, MOLECULAR; ORGANOPHOSPHATES; ORGANOPHOSPHORUS COMPOUNDS; PEPTIDE FRAGMENTS; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, SECONDARY;

EID: 84927646346     PISSN: 15206106     EISSN: 15205207     Source Type: Journal    
DOI: 10.1021/acs.jpcb.5b00692     Document Type: Article

References (54)

1. Prince, M.; Albanese, E.; Guerchet, M.; Prina, M. Alzheimer's Disease International: World Alzheimer Report; 2014.
2. Mattson, M. P. Pathways Towards and Away From Alzheimer's Disease Nature 2004, 430, 631 - 639
3. Selkoe, D. J. Alzheimer's Disease: Genes, Proteins, and Therapy Physiol. Rev. 2001, 81, 741 - 766
4. Jakob-Roetne, R.; Jacobsen, H. Alzheimer's Disease: From Pathology to Therapeutic Approaches Angew. Chem., Int. Ed. 2009, 48, 3030 - 3059
5. Billings, L. M.; Oddo, S.; Green, K. N.; McGaugh, J. L.; LaFerla, F. M. Intraneuronal Aβ Causes the Onset of Early Alzheimer's Disease-related Cognitive Deficits in Transgenic Mice Neuron 2005, 45, 675 - 688
6. Klein, W. L.; Krafft, G. A.; Finch, C. E. Targeting Small Aβ Oligomers: the Solution to an Alzheimer's Disease Conundrum? Trends Neurosci. 2001, 24, 219 - 224
7. Walsh, D. M.; Selkoe, D. J. Aβ Oligomers-a Decade of Discovery J. Neurochem. 2007, 101, 1172 - 1184
8. Shankar, G. M.; Li, S. M.; Mehta, T. H.; Garcia-Munoz, A.; Shepardson, N. E.; Smith, I.; Brett, F. M.; Farrell, M. A.; Rowan, M. J.; Lemere, C. A.; et al. Amyloid-β Protein Dimers Isolated Directly From Alzheimer's Brains Impair Synaptic Plasticity and Memory Nat. Med. 2008, 14, 837 - 842
9. Rahimi, F.; Shanmugam, A.; Bitan, G. Structure-Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimer's Disease and Related Disorders Curr. Alzheimer Res. 2008, 5, 319 - 341
10. Bitan, G.; Kirkitadze, M. D.; Lomakin, A.; Vollers, S. S.; Benedek, G. B.; Teplow, D. B. Amyloid β-protein (Aβ) Assembly: Aβ40 and Aβ42 Oligomerize Through Distinct Pathways Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 330 - 335
11. Teplow, D. B.; Lazo, N. D.; Bitan, G.; Bernstein, S.; Wyttenbach, T.; Bowers, M. T.; Baumketner, A.; Shea, J. E.; Urbanc, B.; Cruz, L.; et al. Elucidating Amyloid β-Protein Folding and Assembly: A Multidisciplinary Approach Acc. Chem. Res. 2006, 39, 635 - 645
12. Bernstein, S. L.; Dupuis, N. F.; Lazo, N. D.; Wyttenbach, T.; Condron, M. M.; Bitan, G.; Teplow, D. B.; Shea, J.-E.; Ruotolo, B. T.; Robinson, C. V.; et al. Amyloid-β Protein Oligomerization and the Importance of Tetramers and Dodecamers in the Aetiology of Alzheimer's Disease Nat. Chem. 2009, 1, 326 - 331
13. Gong, Y.; Chang, L.; Viola, K. L.; Lacor, P. N.; Lambert, M. P.; Finch, C. E.; Krafft, G. A.; Klein, W. L. Alzheimer's Disease-Affected Brain: Presence of Oligomeric Aβ Ligands (ADDLs) Suggests a Molecular Basis for Reversible Memory Loss Proc. Natl. Acad. Sci. U. S. A. 2003, 100, 10417 - 10422
14. Lesné, S.; Koh, M. T.; Kotilinek, L.; Kayed, R.; Glabe, C. G.; Yang, A.; Gallagher, M.; Ashe, K. H. A specific amyloid-β protein assembly in the brain impairs memory Nature 2006, 440, 352 - 357
15. Liu, T.; Bitan, G. Modulating Self-assembly of Amyloidogenic Proteins as a Therapeutic Approach for Neurodegenerative Diseases: Strategies and Mechanisms ChemMedChem 2012, 7, 359 - 374
16. Bateman, R. J.; Siemers, E. R.; Mawuenyega, K. G.; Wen, G.; Browning, K. R.; Sigurdson, W. C.; Yarasheski, K. E.; Friedrich, S. W.; DeMattos, R. B.; May, P. C.; et al. A γ-secretase Inhibitor Decreases Amyloid-β Production in The Central Nervous System Ann. Neurol. 2009, 66, 48 - 54
17. Barten, D.; Meredith, J., Jr.; Zaczek, R.; Houston, J.; Albright, C. γ-Secretase Inhibitors for Alzheimer's Disease Drugs R&D 2006, 7, 87 - 97
18. Imbimbo, P. B.; Giardina, G. A. M. γ-Secretase Inhibitors and Modulators for the Treatment of Alzheimer's Disease: Disappointments and Hopes Curr. Trends Med. Chem. 2011, 11, 1555 - 1570
19. Ghosh, A. K.; Osswald, H. L. BACE1 (β-secretase) Inhibitors for the Treatment of Alzheimer's Disease Chem. Soc. Rev. 2014, 43, 6765 - 6813
20. Bates, K. A.; Verdile, G.; Li, Q. X.; Ames, D.; Hudson, P.; Masters, C. L.; Martins, R. N. Clearance Mechanisms of Alzheimer's Amyloid-β Peptide: Implications for Therapeutic Design and Diagnostic Tests Mol. Psychiatry 2009, 14, 469 - 486
21. Higuchi, M.; Iwata, N.; Saido, T. C. Understanding Molecular Mechanisms of Proteolysis in Alzheimer's Disease: Progress Toward Therapeutic Interventions Biochim. Biophys. Acta, Proteins Proteomic 2005, 1751, 60 - 67
22. Stains, C. I.; Mondal, K.; Ghosh, I. Molecules that Target beta-Amyloid ChemMedChem 2007, 2, 1675 - 1692
23. Necula, M.; Kayed, R.; Milton, S.; Glabe, C. G. Small Molecule Inhibitors of Aggregation Indicate That Amyloid β Oligomerization and Fibrillization Pathways Are Independent and Distinct J. Biol. Chem. 2007, 282, 10311 - 10324
24. Hawkes, C. A.; Ng, V.; McLaurin, J. Small Molecule Inhibitors of Aβ-Aggregation and Neurotoxicity Drug Dev. Res. 2009, 70, 111 - 124
25. Ehrnhoefer, D. E.; Bieschke, J.; Boeddrich, A.; Herbst, M.; Masino, L.; Lurz, R.; Engemann, S.; Pastore, A.; Wanker, E. E. EGCG Redirects Amyloidogenic Polypeptides into Unstructured, Off-pathway Oligomers Nat. Struct. Mol. Biol. 2008, 15, 558 - 566
26. Yang, F. S.; Lim, G. P.; Begum, A. N.; Ubeda, O. J.; Simmons, M. R.; Ambegaokar, S. S.; Chen, P. P.; Kayed, R.; Glabe, C. G.; Frautschy, S. A.; et al. Curcumin Inhibits Formation of Amyloid β Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid In Vivo J. Biol. Chem. 2005, 280, 5892 - 5901
27. McLaurin, J.; Golomb, R.; Jurewicz, A.; Antel, J. P.; Fraser, P. E. Inositol Stereoisomers Stabilize an Oligomeric Aggregate of Alzheimer Amyloid β Peptide and Inhibit Aβ-induced Toxicity J. Biol. Chem. 2000, 275, 18495 - 18502
28. McLaurin, J.; Kierstead, M. E.; Brown, M. E.; Hawkes, C. A.; Lambermon, M. H.; Phinney, A. L.; Darabie, A. A.; Cousins, J. E.; French, J. E.; Lan, M. F.; et al. Cyclohexanehexol Inhibitors of Aβ Aggregation Prevent and Reverse Alzheimer Phenotype in a Mouse Model Nat. Med. 2006, 12, 801 - 808
29. Zheng, X.; Gessel, M. M.; Wisniewski, M. L.; Viswanathan, K.; Wright, D. L.; Bahr, B. A.; Bowers, M. T. Z-Phe-Ala-diazomethylketone (PADK) Disrupts and Remodels Early Oligomer States of the Alzheimer Disease Aβ42 Protein J. Biol. Chem. 2012, 287, 6084 - 6088
30. Fradinger, E. A.; Monien, B. H.; Urbanc, B.; Lomakin, A.; Tan, M.; Li, H.; Spring, S. M.; Condron, M. M.; Cruz, L.; Xie, C.-W.; et al. C-terminal Peptides Coassemble into Aβ42 Oligomers and Protect Neurons Against Aβ42-induced Neurotoxicity Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 14175 - 14180
31. Li, H.; Monien, B. H.; Lomakin, A.; Zemel, R.; Fradinger, E. A.; Tan, M.; Spring, S. M.; Urbanc, B.; Xie, C. W.; Benedek, G. B.; et al. Mechanistic Investigation of the Inhibition of Aβ42 Assembly and Neurotoxicity by Aβ42 C-Terminal Fragments Biochemistry 2010, 49, 6358 - 6364
32. Gessel, M. M.; Wu, C.; Li, H.; Bitan, G.; Shea, J.-E.; Bowers, M. T. Aβ(39-42) Modulates Aβ Oligomerization but Not Fibril Formation Biochemistry 2011, 51, 108 - 117
33. Porat, Y.; Abramowitz, A.; Gazit, E. Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism Chem. Biol. Drug Des. 2006, 67, 27 - 37
34. Attar, A.; Rahimi, F.; Bitan, G. Modulators of Amyloid Protein Aggregation and Toxicity: EGCG and CLR01 Transl. Neurosci. 2013, 4, 385 - 409
35. Lee, S.; Zheng, X.; Krishnamoorthy, J.; Savelieff, M. G.; Park, H. M.; Brender, J. R.; Kim, J. H.; Derrick, J. S.; Kochi, A.; Lee, H. J.; et al. Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer's Disease J. Am. Chem. Soc. 2014, 136, 299 - 310
36. Fokkens, M.; Schrader, T.; Klärner, F.-G. A Molecular Tweezer for Lysine and Arginine J. Am. Chem. Soc. 2005, 127, 14415 - 14421
37. Klärner, F.-G.; Schrader, T. Aromatic Interactions by Molecular Tweezers and Clips in Chemical and Biological Systems Acc. Chem. Res. 2012, 46, 967 - 978
38. Dutt, S.; Wilch, C.; Gersthagen, T.; Talbiersky, P.; Bravo-Rodriguez, K.; Hanni, M.; Sánchez-García, E.; Ochsenfeld, C.; Klärner, F.-G.; Schrader, T. Molecular Tweezers with Varying Anions: A Comparative Study J. Org. Chem. 2013, 78, 6721 - 6734
39. Sinha, S.; Lopes, D. H.; Du, Z.; Pang, E. S.; Shanmugam, A.; Lomakin, A.; Talbiersky, P.; Tennstaedt, A.; McDaniel, K.; Bakshi, R.; et al. Lysine-Specific Molecular Tweezers are Broad-Spectrum Inhibitors of Assembly and Toxicity of Amyloid Proteins J. Am. Chem. Soc. 2011, 133, 16958 - 16969
40. Sinha, S.; Du, Z.; Maiti, P.; Klärner, F. G.; Schrader, T.; Wang, C.; Bitan, G. Comparison of Three Amyloid Assembly Inhibitors: the Sugar Scyllo-Inositol, the Polyphenol Epigallocatechin Gallate, and the Molecular Tweezer CLR01 ACS Chem. Neurosci. 2012, 3, 451 - 458
41. Prabhudesai, S.; Sinha, S.; Attar, A.; Kotagiri, A.; Fitzmaurice, A. G.; Lakshmanan, R.; Ivanova, M. I.; Loo, J. A.; Klärner, F. G.; Schrader, T.; et al. A Novel "Molecular Tweezera" Inhibitor of α-Synuclein Neurotoxicity In Vitro and In Vivo Neurotherapeutics 2012, 9, 464 - 476
42. Attar, A.; Ripoli, C.; Riccardi, E.; Maiti, P.; Li Puma, D. D.; Liu, T.; Hayes, J.; Jones, M. R.; Lichti-Kaiser, K.; Yang, F.; et al. Protection of Primary Neurons and Mouse Brain From Alzheimer's Pathology by Molecular Tweezers Brain 2012, 135, 3735 - 3748
43. Wyttenbach, T.; Kemper, P. R.; Bowers, M. T. Design of a New Electrospray Ion Mobility Mass Spectrometer Int. J. Mass Spectrom. 2001, 212, 13 - 23
44. Wyttenbach, T.; Bowers, M. Gas-Phase Conformations: The Ion Mobility/Ion Chromatography Method. In Modern Mass Spectrometry; Schalley, C., Ed.; Springer: Berlin, Heidelberg, 2003; Vol. 225, pp 207 - 232.
45. Bernstein, S. L.; Wyttenbach, T.; Baumketner, A.; Shea, J.-E.; Bitan, G.; Teplow, D. B.; Bowers, M. T. Amyloid β-Protein: Monomer Structure and Early Aggregation States of Aβ42 and Its Pro19 Alloform J. Am. Chem. Soc. 2005, 127, 2075 - 2084
46. Bleiholder, C.; Dupuis, N. F.; Wyttenbach, T.; Bowers, M. T. Ion Mobility-Mass Spectrometry Reveals a Conformational Conversion from Random Assembly to β-Sheet in Amyloid Fibril Formation Nat. Chem. 2011, 3, 172 - 177
47. Gessel, M. M.; Bernstein, S.; Kemper, M.; Teplow, D. B.; Bowers, M. T. Familial Alzheimer's Disease Mutations Differentially Alter Amyloid β-Protein Oligomerization ACS Chem. Neurosci. 2012, 3, 909 - 918
48. Roychaudhuri, R.; Lomakin, A.; Bernstein, S.; Zheng, X.; Condron, M. M.; Benedek, G. B.; Bowers, M.; Teplow, D. B. Gly25-Ser26 Amyloid β-Protein Structural Isomorphs Produce Distinct Aβ42 Conformational Dynamics and Assembly Characteristics J. Mol. Biol. 2014, 426, 2422 - 2441
49. Baumketner, A.; Bernstein, S. L.; Wyttenbach, T.; Bitan, G.; Teplow, D. B.; Bowers, M. T.; Shea, J.-E. Amyloid β-Protein Monomer Structure: A Computational and Experimental Study Protein Sci. 2006, 15, 420 - 428
50. Bleiholder, C.; Do, T. D.; Wu, C.; Economou, N. J.; Bernstein, S. S.; Buratto, S. K.; Shea, J.-E.; Bowers, M. T. Ion Mobility Spectrometry Reveals the Mechanism of Amyloid Formation of Aβ(25-35) and Its Modulation by Inhibitors at the Molecular Level: Epigallocatechin Gallate and Scyllo-inositol J. Am. Chem. Soc. 2013, 135, 16926 - 16937
51. Lomakin, A.; Chung, D. S.; Benedek, G. B.; Kirschner, D. A.; Teplow, D. B. On the Nucleation and Growth of Amyloid β-Protein Fibrils: Detection of Nuclei and Quantitation of Rate Constants Proc. Natl. Acad. Sci. U. S. A. 1996, 93, 1125 - 1129
52. Gidden, J.; Baker, E. S.; Ferzoco, A.; Bowers, M. T. Structural Motifs of DNA Complexes in the Gas Phase Int. J. Mass Spectrom. 2005, 240, 183 - 193
53. Mason, E. A.; McDaniel, E. W. Transport Properties of Ions in Gases; Wiley: New York, 1988.
54. Lee, H. H.; Choi, T. S.; Lee, S. J. C.; Lee, J. W.; Park, J.; Ko, Y. H.; Kim, W. J.; Kim, K.; Kim, H. I. Supramolecular Inhibition of Amyloid Fibrillation by Cucurbit[7]uril Angew. Chem., Int. Ed. 2014, 53, 7461 - 7465