公开(公告)号：US07220552B1

公开(公告)日：2007-05-22

申请号：US09716054

申请日：2000-11-17

申请人： Gerald R. Crabtree ,  Kryn Stankunas ,  Roger Briesewitz ,  Thomas J. Wandless

发明人： Gerald R. Crabtree ,  Kryn Stankunas ,  Roger Briesewitz ,  Thomas J. Wandless

IPC分类号： G01N33/53 ,  A61K39/00

CPC分类号： G01N33/6845 ,  G01N33/542

摘要： Bifunctional inhibitor molecules and methods for their use in the inhibition of protein—protein interactions are provided. The subject bifunctional inhibitor molecules are conjugates of a target protein ligand and a blocking protein ligand, where these two moieties are optionally joined by a linking group. In the subject methods, an effective amount of the bifunctional inhibitor molecule is administered to a host in which the inhibition of a protein—protein interaction is desired. The bifunctional inhibitor molecule simultaneously binds to its corresponding target and blocking proteins to produce a tripartite complex that inhibits the target protein—protein interaction. The subject methods and compositions find use in a variety of applications, including therapeutic applications.

摘要翻译： 提供了双功能抑制剂分子及其用于抑制蛋白质 - 蛋白质相互作用的方法。 受试者双功能抑制剂分子是靶蛋白配体和阻断蛋白配体的缀合物，其中这两个部分任选地通过连接基团连接。 在本方法中，将有效量的双功能抑制剂分子施用于需要抑制蛋白质 - 蛋白质相互作用的宿主。 双功能抑制剂分子同时结合其相应的靶标和阻断蛋白质以产生抑制靶蛋白 - 蛋白质相互作用的三方复合物。 主题方法和组合物可用于各种应用，包括治疗应用。

公开(公告)号：US20050214738A1

公开(公告)日：2005-09-29

申请号：US10992304

申请日：2004-11-17

申请人： Kryn Stankunas ,  Jason Gestwicki ,  Kelvin Neu ,  Gerald Crabtree ,  Joseph Bayle

发明人： Kryn Stankunas ,  Jason Gestwicki ,  Kelvin Neu ,  Gerald Crabtree ,  Joseph Bayle

IPC分类号： C07H21/04 ,  C07K20060101 ,  C07K14/47 ,  C12N15/00 ,  C12N15/09 ,  C12N15/62 ,  C12N15/85 ,  C12N15/86 ,  C12P21/04 ,  C12Q1/00 ,  G01N33/50

CPC分类号： C07K14/4702 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/03 ,  C07H21/04 ,  C07K2319/95 ,  C12N9/1205 ,  C12N15/62 ,  C12N15/8509 ,  G01N33/5041

摘要： A conditional allelic system is provided where recombinant cells express a fusion protein, where the fusion protein comprises at least a functional portion of a target protein and a destabilizing peptide. The destabilizing peptide binds to a small stabilizing molecule that results in the stabilization of the fusion protein in a functional form, while in the absence of the small stabilizing molecule, the protein function is substantially reduced. The system finds use in studying cellular pathways, preparing transgenic animals that can develop in the presence of the small stabilizing molecule and can then be studied in the presence and absence of the fusion protein to determine the functions and/or effects of target protein function in and/or on various environments. Specifically, a mutated peptide from mTOR is employed as the destabilizing peptide and a modified rapamycin is employed as the small stabilizing molecule.

摘要翻译： 提供条件等位基因系统，其中重组细胞表达融合蛋白，其中融合蛋白包含至少一种靶蛋白的功能部分和去稳定肽。 去稳定肽结合到导致功能性形式的融合蛋白稳定化的小稳定分子，而在不存在小稳定分子的情况下，蛋白质功能显着降低。 该系统用于研究细胞途径，制备可在小稳定分子存在下发展的转基因动物，然后可以在存在和不存在融合蛋白的情况下研究，以确定靶蛋白功能的功能和/或效应 和/或在各种环境中。 具体地，使用来自mTOR的突变肽作为去稳定肽，并且使用修饰的雷帕霉素作为小稳定分子。