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公开(公告)号:US07175828B2
公开(公告)日:2007-02-13
申请号:US10677076
申请日:2003-09-30
申请人: Mark A. Findeis , Malcolm L. Gefter , Gary F. Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
发明人: Mark A. Findeis , Malcolm L. Gefter , Gary F. Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
CPC分类号: C07K5/101 , A61K38/00 , C07K5/1027 , C07K7/06 , C07K14/4711 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要: Compounds that modulate natural β amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a β 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 β amyloid peptide, preferably a retro-inverso isomer of Aβ17-21. 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淀粉样肽的逆反异构体,优选Abeta 17-21的逆反异构体。 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。