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蛋白质精准修饰客体分子的方法

戴震 刘育 刘涛

高等学校化学学报2024,Vol.45Issue(6):59-66,8.
高等学校化学学报2024,Vol.45Issue(6):59-66,8.DOI:10.7503/cjcu20240090

蛋白质精准修饰客体分子的方法

Methodologies for the Precise Modification of Guest Molecules by Proteins

戴震 1刘育 2刘涛3

作者信息

  • 1. 南开大学化学学院,元素有机化学国家重点实验室,天津 300071||北京大学药学院,天然药物及仿生药物国家重点实验室,北京 100191
  • 2. 南开大学化学学院,元素有机化学国家重点实验室,天津 300071
  • 3. 北京大学药学院,天然药物及仿生药物国家重点实验室,北京 100191||北京大学药学院,化学生物学交叉中心,北京 100191||北京大学药学院药学院分子与细胞药理学系,北京 100191
  • 折叠

摘要

Abstract

Precise modification of guest molecules on proteins is a crucial technological foundation for supramole-cular modulation of protein activity.This is especially true for aromatic functional group guests containing positive charges,which can be efficiently bound to cucurbituril.However,precise modification of these molecules on proteins using non-canonical amino acid site specific modification technology can be challenging.The linkers of bioorthogonal reactions are often large,which can affect the recognition of the host and guest molecules.To address this issue,the target proteins were modified by adding iodine-or alkynyl-functional amino acids using the non-canonical amino acid site specific modification technology.The pyridine molecules with a positive charge were efficiently bound to cucurbi-turil molecules using the palladium-catalyzed Suzuki and Sonogashira coupling reaction.Subsequently,a non-natural amino acid with an alkynyl functional group was successfully incorporated into the target proteins using a series of reaction conditions.Furthermore,a Sonogashira coupling reaction was utilized to attach a positively charged pyridine molecule to the protein surface.These accomplishments establish a crucial technological basis for the chemical regulation of proteins through host-guest interactions.

关键词

精准修饰/非天然氨基酸/主客体/蛋白质

Key words

Precise modification/Non-canonical amino acid/Host and guest/Protein

分类

化学化工

引用本文复制引用

戴震,刘育,刘涛..蛋白质精准修饰客体分子的方法[J].高等学校化学学报,2024,45(6):59-66,8.

基金项目

国家自然科学基金(批准号:22325701,U22A20332,92156025,92253301)和国家重点研发计划项目(批准号:2022YFA0912400,2021YFA0909900)和北京市自然科学基金(批准号:JQ20034)的资助. Supported by the National Natural Science Foundation of China(Nos.22325701,U22A20332,92156025,92253301),the National Key Research and Development Program of China(Nos.2022YFA0912400,2021YFA0909900)and the Beijing Natural Science Foundation,China(No.JQ20034). (批准号:22325701,U22A20332,92156025,92253301)

高等学校化学学报

OA北大核心CSTPCD

0251-0790

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