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人工糖蛋白作为靶向药物治疗的支架

Artificial Glycoproteins as a Scaffold for Targeted Drug Therapy.

作者信息

Vong Kenward, Yamamoto Tomoya, Tanaka Katsunori

机构信息

Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.

Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo, 152-8552, Japan.

出版信息

Small. 2020 Jul;16(27):e1906890. doi: 10.1002/smll.201906890. Epub 2020 Feb 18.

Abstract

Akin to a cellular "fingerprint," the glycocalyx is a glycan-enriched cellular coating that plays a crucial role in mediating cell-to-cell interactions. To gain a better understanding of the factors that govern in vivo recognition, artificial glycoproteins were initially created to probe changes made to the accumulation and biodistribution of specific glycan assemblies through biomimicry. As a result, the organ-specific accumulation for a variety of glycoproteins decorated with simple and/or complex glycans was identified. Additionally, binding trends with regard to cancer cell selectivity were also investigated. To exploit the knowledge gained from these studies, numerous groups thus became engaged in developing targeted drug methodologies based on the use of artificial glycoproteins. This has either been done through adopting the glycoprotein scaffold as a drug carrier, or to directly glycosylate therapeutic proteins/enzymes to localize their biological activity. The principle aim of this Review is to present the foundational research that has driven artificial glycoprotein-based targeting and subsequent adaptations with potential therapeutic applications.

摘要

类似于细胞的“指纹”,糖萼是一种富含聚糖的细胞涂层,在介导细胞间相互作用中起着关键作用。为了更好地理解体内识别的调控因素,最初创建了人工糖蛋白,以通过仿生学探究特定聚糖组装体的积累和生物分布变化。结果,确定了多种装饰有简单和/或复杂聚糖的糖蛋白的器官特异性积累。此外,还研究了与癌细胞选择性相关的结合趋势。为了利用这些研究中获得的知识,许多研究团队因此致力于开发基于人工糖蛋白的靶向药物方法。这要么是通过采用糖蛋白支架作为药物载体来实现,要么是直接对治疗性蛋白质/酶进行糖基化以定位其生物活性。本综述的主要目的是介绍推动基于人工糖蛋白的靶向研究以及随后具有潜在治疗应用的适应性研究的基础研究。

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