文献类型：期刊文献

中文题名：Aerolysin纳米孔道探究硫酸乙酰肝素与金属离子的单分子相互作用

英文题名：Single?molecule Investigation of Heparan Sulfate?metal Ion Interactions Using Aerolysin Nanopore

作者：张鹏玲[1];高凡[2];陈嘉乐[6];邹爱华[1];汤娟[3];马慧[4];蒋翠玲[5];万永菁[5];夏冰清[6];李铁海[6];高召兵[6];应佚伦[2];龙亿涛[2]

机构：[1]上海师范大学化学与材料科学学院,上海200234;[2]南京大学化学学院,分子传感与成像中心,南京210023;[3]江西师范大学化学与材料学院,南昌330022;[4]浙江理工大学化学与化工学院,杭州310018;[5]华东理工大学信息科学与工程学院,上海200237;[6]中国科学院上海药物研究所,上海201203

年份：2026

卷号：47

期号：2

起止页码：1

中文期刊名：高等学校化学学报

外文期刊名：Chemical Journal of Chinese Universities

收录：;EI(收录号：20260920149432);WOS:【SCI-EXPANDED(收录号:WOS:001682869300006)】；北大核心:【北大核心2023】；

基金：Supported by the Shanghai Municipal Science and Technology Major Project, China, the National Natural Science Foundation of China (Nos.32250019, 22474055) and the Special Fund for the Basic Scientific Research of Central Universities, China (No.020514380356) .

语种：中文

中文关键词：气单胞菌溶素;单分子分析;纳米孔道;硫酸乙酰肝素;金属离子

外文关键词：Aerolysin;Single-molecule sensing;Nanopore;Heparan sulfate;Metal ion

摘要：肝素(HP)和硫酸乙酰肝素(HS)是一种高度柔性的直链多糖[1],其基本结构单元由交替重复的二糖组成,通常包含一种己糖胺(如N-乙酰-D-葡萄糖胺,GlcNAc)和一种糖醛酸(如D-葡萄糖醛酸,GlcA)[2].值得注意的是,HP/HS中普遍存在多样的磺酸化修饰,包括GlcNAc的N-磺酸化、GlcA的2-O-磺酸化以及GlcNAc的6-O-磺酸化[3].这些修饰赋予了HP/HS高度负电性,因而在与金属离子结合时,不同链段负电荷的空间排列可导致多种局部构象,甚至同一金属离子也可能结合于不同位点,使其能够与多种蛋白质发生特异性相互作用,从而在细胞生长[4]、炎症反应[5]和肿瘤抑制[6]等过程中发挥关键作用.因此,揭示HP/HS与不同金属离子的相互作用机制,对于深入理解其生物学功能具有重要意义[7~9].
Heparin(HP)and heparan sulfate(HS)are highly anionic glycosaminoglycans that play essential roles in diverse biological processes through the metal ion-mediated interactions with proteins.However,direct characteriza?tion of HS-metal ion interactions at the single-molecule level in solution remains challenging.Nanopore electrochemis?try is a label-free and single-molecule technique that enables direct analysis of individual molecular interactions.In this study,a T 232 K/K 238 Q Aerolysin nanopore featuring an enhanced electrostatic repelling barrier was utilized to probe the interactions between HS and different metal ions.By systematically varying the electrolyte cations(Na+,K+,and Ca 2+),we have found that the metal ions significantly regulate HS translocation behavior by modulating its conformation,charge screening,and HS-nanopore interactions.Notably,in addition to Ca 2+,which exhibits strong binding affinity to HS,the monovalent cations Na?and K?with similar physicochemical properties and weaker binding also induce distinct single-molecule signal signatures.Our results demonstrate that the nanopore-based single-molecule analysis holds strong potential to resolve the fine structural features of HS,enabling the characteriza?tion of sulfation site distributions,repeat-unit lengths,and related sequence features,and thereby providing a new avenue for high-resolution analysis of complex glycans.