公开(公告)号：US07803774B2

公开(公告)日：2010-09-28

申请号：US10989763

申请日：2004-11-15

申请人： Mark A. Findeis ,  Kathryn Phillips ,  Gary L. Olsen ,  Christopher Self

发明人： Mark A. Findeis ,  Kathryn Phillips ,  Gary L. Olsen ,  Christopher Self

IPC分类号： A61K38/00 ,  A61K49/00

CPC分类号： C07K14/4711 ,  A61K38/00

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 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.

摘要翻译： 调节天然化合物的化合物 提供淀粉样肽聚集。 本发明的调节剂包含肽，优选基于 淀粉样肽，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。 在一个特别优选的实施方案中，该肽是一种反式异构体， 淀粉样蛋白肽，优选A-Bgr; 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是烷基。 优选的羧基末端修饰基团包括酰胺基，乙酸基，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。