Custom chemical microarray production and affinity fingerprinting for the S1 pocket of factor VIIa
Custom chemical microarray production and affinity fingerprinting for the S1 pocket of factor VIIa
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DOI：
10.1016/j.ab.2004.08.033
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发表时间：
2004-12-01
影响因子：
2.9
通讯作者：
Nestler, HP
中科院分区：
文献类型：
--
作者：
Dickopf, S;Frank, M;Nestler, HP
本研究的目的是探索基于表面等离子体共振（SPR）的片段筛选在识别与因子VIIa （FVIIa）结合的化合物中的适用性。基于药效团模型虚拟筛选方法，我们选择了预期有合理机会与FVIIa的s1结合口袋结合的片段，并将这些化合物固定在微阵列上。在亲和指纹图谱实验中，许多化合物被鉴定为与FVIIa特异性相互作用，并被显示为四种结构类别。结果表明，使用SPR检测的化学微阵列技术平台可生成独特的化学生物学信息，可用于从头发现和先导物开发，并允许检测与低分子量配体的弱相互作用。(C) 2004爱思唯尔公司版权所有。
The goal of this study was to explore the applicability of surface plasmon resonance (SPR)-based fragment screening to identify compounds that bind to factor VIIa (FVIIa). Based on pharmacophore models virtual screening approaches, we selected fragments anticipated to have a reasonable chance of binding to the S1-binding pocket of FVIIa and immobilized these compounds on microarrays. In affinity fingerprinting experiments, a number of compounds were identified to be specifically interacting with FVIIa and shown to fall into four structural classes. The results demonstrate that the chemical microarray technology platform using SPR detection generates unique chemobiological information that is useful for de novo discovery and lead development and allows the detection of weak interactions with ligands of low molecular weight. (C) 2004 Elsevier Inc. All rights reserved.