Modulators of &bgr;-amyloid peptide aggregation comprising D-amino acids

US6689752B2 · kind B2 · utility

Assignee

• Praecis Pharmaceuticals, Inc. · US

Inventors

• Mark A. Findeis · Belmont, US
• Malcolm L. Gefter · Lincoln, US
• Gary Musso · Hopkinton, US
• Ethan R. Signer · Cambridge, US
• James Wakefield · Brookline, US
• Susan Molineaux · San Francisco, US
• Joseph Chin · Salem, US
• Jung-Ja Lee · Wayland, US
• Michael Kelley · Arlington, US
• Sonja Komar-Panicucci · Bedford, US
• Christopher C. Arico-Muendel · Watertown, US
• Kathryn Phillips · Boston, US
• Neil J. Hayward · Westborough, US

Key dates

• Filing date: Jun 29, 2001
• Grant date: Feb 10, 2004
• Expiry date: Jun 29, 2021

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2800/2821
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. 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.