Dickopf Stefan, Frank Michael, Junker Hans-Dieter, Maier Sabine, Metz Günther, Ottleben Holger, Rau Harald, Schellhaas Nathalie, Schmidt Kristina, Sekul Renate, Vanier Cecile, Vetter Dirk, Czech Jörg, Lorenz Martin, Matter Hans, Schudok Manfred, Schreuder Herman, Will David W, Nestler Hans Peter
Graffinity Pharmaceuticals AG, Im Neuenheimer Feld 518-519, D-69120 Heidelberg, Germany.
Anal Biochem. 2004 Dec 1;335(1):50-7. doi: 10.1016/j.ab.2004.08.033.
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.
本研究的目的是探索基于表面等离子体共振（SPR）的片段筛选在鉴定与凝血因子VIIa（FVIIa）结合的化合物方面的适用性。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。在亲和指纹实验中，鉴定出许多与FVIIa特异性相互作用的化合物，并显示它们分为四类结构。结果表明，使用SPR检测的化学微阵列技术平台产生了独特的化学生物学信息，这对于从头发现和先导物开发很有用，并允许检测与低分子量配体的弱相互作用。
