Currently, there are no methods available offering solutions to select and identify antibodies binding to a specific conformational epitope of an antigen. Here, we developed a method to allow epitope-directed antibody selection from a phage display library by photocrosslinking bound antibodies to a site that specifically incorporates a noncanonical amino acid, p-benzoyl-l-phenylalanine (pBpa), on the target antigen epitope. By one or two rounds of panning against antibody phage display libraries, those hits that covalently bind to the proximity site of pBpa on specific epitopes of target antigens after ultraviolet irradiation are enriched and selected. This method was applied to specific epitopes on human interleukin-1β and complement 5a. In both cases, more than one-third of hits identified bind to the target epitopes, demonstrating the feasibility and versatility of this method.

中文翻译：

---

通过位点特异性光交联进行表位指导的抗体选择。

当前，没有可用的方法提供选择和鉴定与抗原的特定构象表位结合的抗体的解决方案。在这里，我们开发了一种方法，可通过使结合的抗体与目标抗原表位上的非典型氨基酸对苯甲酰基-1-苯丙氨酸（pBpa）特异性结合的位点进行光交联，从噬菌体展示库中选择表位指导的抗体。通过一轮或两轮针对抗体噬菌体展示文库的淘选，富集并选择了在紫外线照射后共价结合至目标抗原特定表位上pBpa邻近位点的命中物。该方法应用于人白介素-1β和补体5a上的特定表位。在这两种情况下，超过三分之一的匹配均与目标表位结合，