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碳水化合物的基因编码化学交联
作者:小柯机器人 发布时间:2022/10/12 20:48:24

美国加州大学旧金山分校Wang Lei团队报道了碳水化合物的基因编码化学交联。相关研究成果发表在2022年10月10日出版的《自然—化学》。

蛋白质-碳水化合物相互作用在各种生物过程中发挥着重要作用,例如生物体发育、癌症转移、病原体感染和免疫反应,但由于其结合亲和力低和非共价性质,它们的研究和开发仍然具有挑战性。

该文中,研究人员在生物相容性条件下定位了蛋白质和碳水化合物之间的特异性共价键。研究表明,磺酰氟与聚糖通过邻近激活的反应性发生反应,为了利用这种反应,含有磺酰氟化物的生物活性非天然氨基酸(SFY)被遗传编码到蛋白质中。SFY包覆的Siglec-7在体外和癌细胞表面特异性地与其唾液聚糖配体交联。通过在癌细胞表面不可逆转地隐藏唾液聚糖,SFY包覆的Siglec-7增强了自然杀伤细胞对癌细胞的杀伤作用。蛋白质与碳水化合物的化学交联(GECX糖)的基因编码,为解决蛋白质与糖之间的低亲和力和弱强度相互作用提供了解决方案。

附:英文原文

Title: Genetically encoded chemical crosslinking of carbohydrate

Author: Li, Shanshan, Wang, Nanxi, Yu, Bingchen, Sun, Wei, Wang, Lei

Issue&Volume: 2022-10-10

Abstract: Protein–carbohydrate interactions play important roles in various biological processes, such as organism development, cancer metastasis, pathogen infection and immune response, but they remain challenging to study and exploit due to their low binding affinity and non-covalent nature. Here we site-specifically engineered covalent linkages between proteins and carbohydrates under biocompatible conditions. We show that sulfonyl fluoride reacts with glycans via a proximity-enabled reactivity, and to harness this a bioreactive unnatural amino acid (SFY) that contains sulfonyl fluoride was genetically encoded into proteins. SFY-incorporated Siglec-7 crosslinked with its sialoglycan ligand specifically in vitro and on the surface of cancer cells. Through irreversible cloaking of sialoglycan at the cancer cell surface, SFY-incorporated Siglec-7 enhanced the killing of cancer cells by natural killer cells. Genetically encoding the chemical crosslinking of proteins to carbohydrates (GECX-sugar) offers a solution to address the low affinity and weak strength of protein–sugar interactions.

DOI: 10.1038/s41557-022-01059-z

Source: https://www.nature.com/articles/s41557-022-01059-z

期刊信息

Nature Chemistry:《自然—化学》,创刊于2009年。隶属于施普林格·自然出版集团,最新IF:21.687
官方网址:https://www.nature.com/nchem/
投稿链接:https://mts-nchem.nature.com/cgi-bin/main.plex