公开(公告)号：US5985242A

公开(公告)日：1999-11-16

申请号：US920162

申请日：1997-08-27

申请人： Mark A. Findeis ,  Malcolm L. Gefter ,  Gary Musso ,  Ethan R. Signer ,  James Wakefield ,  Susan Molineaux ,  Joseph Chin ,  Jung-Ja Lee ,  Michael Kelley ,  Sonja Komar-Panicucci ,  Christopher C. Arico-Muendel ,  Kathryn Phillips ,  Neil J. Hayward

发明人： Mark A. Findeis ,  Malcolm L. Gefter ,  Gary Musso ,  Ethan R. Signer ,  James Wakefield ,  Susan Molineaux ,  Joseph Chin ,  Jung-Ja Lee ,  Michael Kelley ,  Sonja Komar-Panicucci ,  Christopher C. Arico-Muendel ,  Kathryn Phillips ,  Neil J. Hayward

IPC分类号： A61K38/00 ,  C07K14/47 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08 ,  C07K7/06

CPC分类号： C07K14/4711 ,  A61K38/00

摘要： 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.

摘要翻译： 提供调节天然β淀粉样肽聚集的化合物。 本发明的调节剂包含优选基于β-淀粉样肽的肽，其完全由D-氨基酸组成。 优选地，肽包含3-5个D-氨基酸残基，并且包括独立地选自D-亮氨酸，D-苯丙氨酸和D-缬氨酸的至少两个D-氨基酸残基。 在特别优选的实施方案中，肽是β淀粉样蛋白肽的逆反异构体，优选Aβ17-21的逆反式异构体。 在某些实施方案中，肽在氨基末端，羧基末端或两者都被修饰。 优选的氨基末端修饰基团包括环状，杂环，多环和支链烷基。 优选的羧基末端修饰基团包括酰胺基，烷基酰胺基，芳基酰胺基或羟基。 还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。