Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing
Patent
1997-08-27
1999-11-16
Russel, Jeffrey E.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
424 942, 424 945, 436501, 514 17, 514 18, 530330, 530331, A61K 3806, A61K 3807, A61K 3808, C07K 706
Patent
active
059852429
ABSTRACT:
Compounds that modulate natural .beta. amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a .beta. 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 .beta. amyloid peptide, preferably a retro-inverso isomer of A.beta..sub.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.
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Arico-Muendel Christopher C.
Chin Joseph
Findeis Mark A.
Gefter Malcolm L.
Hayward Neil J.
DeConti, Jr. Guilio A.
Mandragouras Amy E.
Praecis Pharmaceuticals Inc.
Russel Jeffrey E.
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