Department of Antibody Discovery and Protein Engineering, MedImmune Ltd, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK.
BioDrugs. 2018 Aug;32(4):339-355. doi: 10.1007/s40259-018-0289-y.
Cell surface membrane proteins comprise a wide array of structurally and functionally diverse proteins involved in a variety of important physiological and homeostatic processes. Complex integral membrane proteins, which are embedded in the lipid bilayer by multiple transmembrane-spanning helices, are represented by families of proteins that are important target classes for drug discovery. Such protein families include G-protein-coupled receptors, ion channels and transporters. Although these targets have typically been the domain of small-molecule drugs, the exquisite specificity of monoclonal antibodies offers a significant opportunity to selectively modulate these target proteins. Nevertheless, the isolation of antibodies with desired pharmacological functions has proved difficult because of technical challenges in preparing membrane protein antigens for antibody drug discovery. In this review, we describe recent progress in defining strategies for the generation of membrane protein antigens. We also describe antibody-isolation strategies that identify antibodies that bind the membrane protein and modulate protein function.
细胞膜蛋白包含广泛的结构和功能多样化的蛋白质，参与多种重要的生理和动态平衡过程。复杂的整合膜蛋白通过多个跨膜螺旋嵌入脂质双层中，由一系列对药物发现很重要的蛋白质家族代表。这类蛋白质家族包括 G 蛋白偶联受体、离子通道和转运蛋白。尽管这些靶点通常是小分子药物的领域，但单克隆抗体的高度特异性为选择性调节这些靶蛋白提供了一个重要机会。然而，由于在为抗体药物发现制备膜蛋白抗原方面存在技术挑战，因此获得具有所需药理功能的抗体一直很困难。在这篇综述中，我们描述了定义生成膜蛋白抗原策略的最新进展。我们还描述了抗体分离策略，这些策略可以识别与膜蛋白结合并调节蛋白功能的抗体。
