公开(公告)号：US5543498A

公开(公告)日：1996-08-06

申请号：US417279

申请日：1995-04-05

申请人： Mark C. Fishman ,  Michihiro Igarashi ,  Stephen M. Strittmatter

发明人： Mark C. Fishman ,  Michihiro Igarashi ,  Stephen M. Strittmatter

IPC分类号： A61K38/00 ,  C07K14/47 ,  A61K38/04 ,  C07K7/06

CPC分类号： C07K14/4702 ,  A61K38/00

摘要： Inhibition of nerve growth normally helps to prevent aberrant pathway or target selection, but also prevents needed regeneration in the mammalian central nervous system. The responsible inhibitory ligands are unknown, but pertussis toxin-sensitive G proteins, which are enriched in growth cones, appear to be involved in causing the responding growth cones to collapse. GAP-43 is an intracellular protein that can amplify the response to the stimulation of G protein-coupled receptors. We have attempted to modify the sensitivity of nerves to inhibitory signals by the use of GAP-43 peptides. The peptide corresponding to the native amino terminus sequence stimulates G.sub.o and enhances the growth cone collapse induced by inhibitory ligands. Modification of two critical cysteines generates peptides which inhibit G.sub.o and which markedly reduce the degree of inhibitor-mediated growth cone collapse.

摘要翻译： 抑制神经生长通常有助于防止异常途径或靶标选择，而且可以防止哺乳动物中枢神经系统中需要的再生。 负责的抑制性配体是未知的，但是富含生长锥的百日咳毒素敏感的G蛋白似乎涉及引起响应的生长锥体崩溃。 GAP-43是可以扩增对G蛋白偶联受体刺激反应的细胞内蛋白质。 我们试图通过使用GAP-43肽来改变神经对抑制性信号的敏感性。 对应于天然氨基末端序列的肽刺激Go，并增强由抑制性配体诱导的生长锥塌陷。 两个关键半胱氨酸的修饰产生抑制Go的肽，并显着降低抑制剂介导的生长锥体崩溃的程度。