公开(公告)号：US06797460B2

公开(公告)日：2004-09-28

申请号：US09930600

申请日：2001-08-15

申请人： Daniel S. Sem ,  Maurizio Pellecchia ,  Anna Tempczyk-Russell

发明人： Daniel S. Sem ,  Maurizio Pellecchia ,  Anna Tempczyk-Russell

IPC分类号： C12Q100

CPC分类号： C12Q1/00 ,  C12Q1/32 ,  C12Q1/485 ,  G01N33/53 ,  G01N33/542 ,  G01N33/6803 ,  G01N2500/00 ,  G01N2500/20 ,  Y10T436/24

摘要： Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

摘要翻译： 用于快速鉴定可以在共同配体位点和特异性配体位点处结合酶的候选药物的方法，导致高亲和力结合。 双重配体药物候选物从聚焦的组合文库筛选，其中优化核心结构上的特异性变异点。 通过与共同配体位点结合的配体的哪个原子被鉴定为接近特异性配体位点来鉴定最佳的变化点。 结果，接近特异性配体位点的原子然后可以用作变异点，以产生可以结合共同配体位点和特异性配体位点的高亲和力药物候选物的聚焦组合文库。 然后，文库中的不同候选物可以对共享相似共同配体位点的许多相关酶具有高亲和力。