申请人:——
公开号:US20030186901A1
公开(公告)日:2003-10-02
The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75
NTR
common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75
NTR
comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys
34
of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys
95
of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys
88
of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys
32
of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile
31
, Phe
101
and Phe
86
of nerve growth factor.
本发明涉及一种抑制神经生长因子与p75NTR共同神经营养因子受体结合的组合物及其使用方法。在一种实施方式中,抑制神经生长因子与p75NTR结合的化合物,特别是当与神经生长因子结合时,至少包含以下两个中的两个:(1)第一个电负原子或功能基位于与神经生长因子的Lys34相互作用的位置;(2)第二个电负原子或功能基位于与神经生长因子的Lys95相互作用的位置;(3)第三个电负原子或功能基位于与神经生长因子的Lys88相互作用的位置;(4)第四个电负原子或功能基位于与神经生长因子的Lys32相互作用的位置;以及(5)与Ile31,Phe101和Phe86形成的疏水区域相互作用的疏水基团。