Methods for Engineering Binders to Multi-Pass Membrane Proteins.

Methods for Engineering Binders to Multi-Pass Membrane Proteins.
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DOI:
10.3390/bioengineering10121351
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发表时间:
2023-11-24
期刊:
Bioengineering (Basel, Switzerland)
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其他
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许多潜在的药物靶点,包括G蛋白偶联受体和离子通道蛋白,作为多通道膜蛋白存在于细胞表面。不幸的是,尽管工程技术取得了进展,但针对多通道膜蛋白的工程生物制剂仍然是一项艰巨的任务。在这篇综述中,我们重点介绍了用于制备/呈现多通道跨膜蛋白的不同方法,用于工程靶向特异性生物制剂,如抗体,纳米抗体和合成支架蛋白。这些工程生物制剂具有高度的特异性和亲和力,在治疗药物、细胞染色探针和促进蛋白质结晶的分子伴侣等方面有着广泛的应用。我们主要涵盖了过去10年来关于这一主题的出版物,重点是不同形式的多通道跨膜蛋白。最后,这一领域所面临的挑战和新技术的开发,以克服一些障碍进行了讨论。
Numerous potential drug targets, including G-protein-coupled receptors and ion channel proteins, reside on the cell surface as multi-pass membrane proteins. Unfortunately, despite advances in engineering technologies, engineering biologics against multi-pass membrane proteins remains a formidable task. In this review, we focus on the different methods used to prepare/present multi-pass transmembrane proteins for engineering target-specific biologics such as antibodies, nanobodies and synthetic scaffold proteins. The engineered biologics exhibit high specificity and affinity, and have broad applications as therapeutics, probes for cell staining and chaperones for promoting protein crystallization. We primarily cover publications on this topic from the past 10 years, with a focus on the different formats of multi-pass transmembrane proteins. Finally, the remaining challenges facing this field and new technologies developed to overcome a number of obstacles are discussed.
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