Complex integral membrane proteins, which are embedded in the cell surface lipid bilayer by multiple transmembrane spanning helices, encompass families of proteins which are important target classes for drug discovery. These protein families include G protein-coupled receptors, ion channels and transporters. Although these proteins have typically been targeted by small molecule drugs and peptides, the high specificity of monoclonal antibodies offers a significant opportunity to selectively modulate these target proteins. However, it remains the case that isolation of antibodies with desired pharmacological function(s) has proven difficult due to technical challenges in preparing membrane protein antigens suitable to support antibody drug discovery. In this review recent progress in defining strategies for generation of membrane protein antigens is outlined. We also highlight antibody isolation strategies which have generated antibodies which bind the membrane protein and modulate the protein function.

中文翻译：

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生成针对复杂多跨膜靶标的治疗性单克隆抗体：克服抗原挑战并启用发现策略

复杂的整合膜蛋白，通过多个跨膜螺旋嵌入细胞表面脂质双层，包括蛋白质家族，它们是药物发现的重要目标类别。这些蛋白质家族包括 G 蛋白偶联受体、离子通道和转运蛋白。尽管这些蛋白质通常被小分子药物和肽靶向，但单克隆抗体的高特异性为选择性调节这些靶蛋白提供了重要的机会。然而，由于制备适合支持抗体药物发现的膜蛋白抗原的技术挑战，分离具有所需药理学功能的抗体仍然是困难的。在这篇综述中，概述了定义膜蛋白抗原生成策略的最新进展。我们还强调了抗体分离策略，这些策略产生了结合膜蛋白并调节蛋白质功能的抗体。