Praecis Pharmaceuticals, Inc.

Gary L Olsen

Christopher Self

Mark A Findeis

Kathryn Phillips

Compounds that modulate natural &#x3b2; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &#x3b2; 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 &#x3b2; amyloid peptide, preferably a retro-inverso isomer of A&#x3b2;. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an acetate 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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Mountainside, NJ, United States of America

Gary L Olsen