Department of Chemical & Systems Biology and ChEM-H, Stanford School of Medicine, Stanford, CA, USA.
Department of Chemistry, Stanford University, Stanford, CA, USA.
Nat Rev Drug Discov. 2021 Mar;20(3):217-243. doi: 10.1038/s41573-020-00093-1. Epub 2021 Jan 18.
Carbohydrates - namely glycans - decorate every cell in the human body and most secreted proteins. Advances in genomics, glycoproteomics and tools from chemical biology have made glycobiology more tractable and understandable. Dysregulated glycosylation plays a major role in disease processes from immune evasion to cognition, sparking research that aims to target glycans for therapeutic benefit. The field is now poised for a boom in drug development. As a harbinger of this activity, glycobiology has already produced several drugs that have improved human health or are currently being translated to the clinic. Focusing on three areas - selectins, Siglecs and glycan-targeted antibodies - this Review aims to tell the stories behind therapies inspired by glycans and to outline how the lessons learned from these approaches are paving the way for future glycobiology-focused therapeutics.
碳水化合物——即糖链——修饰着人体的每一个细胞和大多数分泌蛋白。基因组学、糖蛋白质组学和化学生物学工具的进步使糖生物学更易于研究和理解。糖基化失调在从免疫逃逸到认知的疾病过程中起着重要作用，激发了旨在针对糖链获得治疗益处的研究。该领域现在正准备在药物开发方面取得突破。作为这种活动的先兆，糖生物学已经产生了几种改善人类健康的药物，或者目前正在向临床转化。本文聚焦于三个领域——选择素、Siglecs 和糖基靶向抗体，旨在讲述受糖启发的疗法背后的故事，并概述从这些方法中吸取的经验教训如何为未来以糖生物学为重点的治疗方法铺平道路。
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