Modulators of amyloid aggregation

Details Modulators of amyloid aggregation Modulators of amyloid aggregation

2003-06-17

2010-02-09

Russel, Jeffrey E (Department: 1654)

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Stabilized enzymes or enzymes complexed with nonenzyme

C424S094610, C435S188000, C435S206000, C514S007600, C514S012200, C514S021800, C530S307000, C530S324000, C530S345000, C530S350000, C530S359000, C530S382000, C530S394000, C530S402000, C530S410000

Reexamination Certificate

active

07658917

ABSTRACT:
Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural β amyloid peptides (β-AP). In a preferred embodiment, the β amyloid modulator compounds of the invention are comprised of an Aβ aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural β amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural β-AP aggregation when the natural β-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

REFERENCES:
patent: 5338663 (1994-08-01), Potter et al.
patent: 5470951 (1995-11-01), Roberts
patent: 5817626 (1998-10-01), Findeis et al.
patent: 5854215 (1998-12-01), Findeis et al.
patent: 6319498 (2001-11-01), Findeis et al.
patent: 0554887 (1993-08-01), None
patent: 0681844 (1995-11-01), None
patent: 0641861 (2003-04-01), None
patent: WO-93/04194 (1993-03-01), None
patent: WO-94/28412 (1994-12-01), None
patent: WO-95/05394 (1995-02-01), None
patent: WO-95/05604 (1995-02-01), None
patent: WO-95/12815 (1995-05-01), None
patent: WO-95/20979 (1995-08-01), None
Chantry et al. Biotinyl analogues of amylin . . . FEBS Letters. Jan. 1992. vol. 296, No. 2, pp. 123-127.
Saito et al. Vector-Mediated Delivery . . . Proceedings of the National Academy of Sciences USA. Oct. 1995, vol. 92, No. 22, pp. 10227-10231.
Koudinov et al. The Soluble Form Of Alzheimer's Amyloid Beta Protein. Biochemical and Biophysical Research Communications. Dec. 15, 1994, vol. 205, No. 2, pp. 1164-1171.
Barrow, Colin J. and Michael G. Zagorski (1991) “Solution Structures of β Peptide and Its Constituent Fragments: Relation to Amyloid Deposition”Science253: 179-182.
Barrow, Colin J. et al. (1992) “Solution Conformations and Aggregational Properties of Synthetic Amyloid β-Peptides of Alzheimer's Disease: Analysis of Circular Dichroism Spectra”J. Mol. Biol. 225: 1075-1093.
Brown, Abraham M. et al. (1994) “Biotinylated and Cysteine-Modified Peptides as Useful Reagents for Studying the Inhibition of Cathepsin G”Analytical Biochemistry217: 139-147.
Burdick, Debra et al. (1992) “Assembly and Aggregation Properties of Synthetic Alzheimer's A4/β Amyloid Peptide Analogs”Journal of Biological Chemistry267(1): 546-554.
Chantry, Andrew et al. (1992) “Biotinyl Analogues of Amylin as Biologically Active Probes for Amylin/CGRP Receptor Recognition”FEBS296(2): 123-127.
Clements, Angela et al. (1993) “Aggregation of Alzheimer's Peptides”Biochemical Society Transactions22: 16S.
Come, Jon H. et al. (1993) “A Kinetic Model for Amyloid Formation in the Prion Diseases: Importance of Seeding”Proc. Natl. Acad. Sci. USA90: 5959-5963.
Evans, Krista C. et al. (1995) “Apolipoprotein E Is a Kinetic But Not a Thermodynamic Inhibitor of Amyloid Formation: Implications for the Pathogenesis and Treatment of Alzheimer Disease”Proc. Natl. Acad. Sci. USA92: 763-767.
Fabian, Heinz et al. (1993) “Comparative Analysis of Human and Dutch-Type Alzheimer β-Amyloid Peptides by Infrared Spectroscopy and Circular Dichroism”Biochemical and Biophysical Research Communications191(1): 232-239.
Fabian, Heinz et al. (1994) “Synthetic Post-Translationally Modified Human Aβ Peptide Exhibits a Markedly Increased Tendency to Form β-Pleated Sheets in vitro”Eur. J. Biochem. 221: 959-964.
Flood, J. et al. (1994) “Topography of a Binding Site for Small Amnestic Peptides Deduced from Structure-activity Studies: Relation to Amnestic Effect of Amyloid β Protein,”PNAS, 91:380-4.
Fraser, Paul E. et at. (1994) “Conformation and Fibrillogenesis of Alzheimer Aβ Peptides with Selected Substitution of Charged Residues”J. Mol. Biol. 244: 64-73.
Fraser, Paul E. et al. (1992) “Fibril Formation by Primate, Rodent, and Dutch-Hemorrhagic Analogues of Alzheimer Amyloid β-Protein”Biochemistry31: 10716-10723.
Gorevic, PD et al. (1987) “Ten to Fourteen Residue Peptides of Alzheimer's Disease Protein are Sufficient for Amyloid Fibril Formation and Its Characteristic Xray Diffraction Pattern”Biochemical and Biophysical Research Communications147(2): 854-862.
Gowing, Eric et al. (1994) “Chemical Characterization of Aβ 17-42 Peptide, a Component of Diffuse Amyloid Deposits of Alzheimer Disease”J. Biol. Chem. 269(15): 10987-10990.
Halverson, Kurt et at. (1990) “Molecular Determinants of Amyloid Deposition in Alzheimer's Disease: Conformational Studies of Synthetic β-Protein Fragments”Biochemistry29(11): 2639-2644.
Hansen, Morten B. et at. (1989) “Re-examination and Further Development of a Precise and Rapid Dye Method for Measuring Cell Growth/Cell Kill”J. Immunol. Meth. 119: 203-210.
Hardy, John A. and Gerald A. Higgins (1992) “Alzheimer's Disease: The Amyloid Cascade Hypothesis”Science256: 184-185.
Hilbich, Caroline et al. (1991) “Aggregation and Secondary Structure of Synthetic Amyloid βA4 Peptides of Alzheimer's Disease”J. Mol. Biol. 218: 149-163.
Hilbich, Caroline et al. (1991) “Human and Rodent Sequence Analogs of Alzheimer's Amyloid βA4 Share Similar Properties and Can Be Solubilized in Buffers of pH 7.4”Eur. J. Biochem. 201: 61-69.
Hilibich, Caroline et al., (1992) “Substitutions of Hydrophobic Amino Acids Reduce the Amyloidogenicity of Alzheimer's Disease βA4 Peptides,” J. Mol. Biol, vol. 228:460-473.
Inouye, H. et al, (1993) “Structure of Beta-Crystallite Assemblies Formed by Alzheimer β-Amyloid Protein Analogs: Analysis by X-ray Diffraction,”Chemical Abstracts, vol. 119:349, Abstract No. 119.
Jarrett, Joseph T. and Peter T. Lansbury, Jr. (1993) “Seeding ‘One-Dimensional Crystallization’ of Amyloid: A Pathogenic Mechanism in Alzheimer's Disease and Scrapie?”Cell73: 1055-1058.
Jarrett, Joseph T. et al. (1993) “The Carboxy Terminus of the β Amyloid Protein Is Critical for the Seeding of Amyloid Formation: Implications for the Pathogenesis of Alzheimer's Disease”Biochemistry32(18): 4693-4697.
Jarrett, Joseph T. et al. (1994) “Models of the β Protein C-Terminus: Differences in Amyloid Structure May Lead to SEgregation of ‘Long’ and ‘Short’ Fibrils”Journal of the American Chemical Society, vol. 116(21):9741-9742.
Kelly, Jeffery W. and Peter T. Lansbury, Jr. (1994) “A Chemical Approach to Elucidate the Mechanism of Transthyretin and β-Protein Amyloid Fibril Formation”Int. J. Exp. Clin. Invest1: 186-205.
Kirschner, Daniel A. et al. (1987) “Synthetic Peptide Homologous to βProtein from Alzheimer Disease forms Amyloid-like Fibrils in vitro”Proc. Natl. Acad. Sci. USA84: 6953-6957.
Klunk, William E. and Jay W. Pettegrew (1990) “Alzheimer's β-Amyloid Protein Is Covalently Modified When Dissolved in Formic Acid”Journal of Neurochemistry54(6): 2050-2054.
Lansbury, Jr., Peter T. (1992) “In Pursuit of the Molecular Structure of Amyloid Plaque: New Technology Provides Unexpected and Critical Information”Biochemistry31(30): 6866-6870.
LeVine, III, Harry (1993) “Thioflavine T Interaction with Synthetic Alzheimer's Disease β-Amyloid Peptides: Detection of Amyloid Aggregation in Solution”Protein Science2: 404-410.
Maggio, John E. et al. (1992) “Reversible in vitro Growth of Alzheimer Disease β-Amyloid Plaques by Dep

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