A peptoid "Antibody surrogate" that antagonizes VEGF receptor 2 activity
A peptoid "Antibody surrogate" that antagonizes VEGF receptor 2 activity
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DOI：
10.1021/ja711193x
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发表时间：
2008-04-30
影响因子：
15
通讯作者：
Kodadek, Thomas
中科院分区：
文献类型：
--
作者：
Udugamasooriya, D. Gomika;Dineen, Sean P.;Kodadek, Thomas
我们报道了一种基于细胞的双色筛选方法，用于在展示于微珠上的类肽组合文库中鉴定特异性受体结合化合物。我们将这一策略应用于血管内皮生长因子受体2（VEGFR2）结合类肽的分离。其中一种先导化合物的二聚体衍生物在体外和体内均被证明是VEGFR2活性的拮抗剂。这种方法为合成能与整合膜受体结合且亲和力和特异性类似于抗体，但尺寸更小、更易于制备和操作的分子提供了一种潜在的通用途径。
We report a two-color, cell-based screen to identify specific receptor-binding compounds in a combinatorial library of peptoids displayed on beads. We apply this strategy to the isolation of vascular endothelial growth factor receptor 2 (VEGFR2)-binding peptoids. A dimeric derivative of one of these lead compounds is shown to be an antagonist of VEGFR2 activity both in vitro and in vivo. This methodology provides a potentially general route to synthetic molecules that bind integral membrane receptors with affinities and specificities similar to those of antibodies, but which are far smaller and easier to make and manipulate.