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2024 , Vol. 44 >Issue 11: 3417 - 3426

DOI: https://doi.org/10.6023/cjoc202404028

研究论文

激活型近红外荧光探针用于肝癌中二肽基肽酶活性检测

  • 张飞 ,
  • 梅煜 ,
  • 丁雪峰 ,
  • 李再峰 ,
  • 张鹏 ,
  • 丁彩凤
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  • 青岛科技大学化学与分子工程学院 光电传感与生命分析教育部重点实验室 山东省生化分析重点实验室 山东省生命分析高校重点实验室 山东青岛 266042

收稿日期: 2024-04-19

  修回日期: 2024-05-20

  网络出版日期: 2024-06-13

基金资助

国家自然科学基金(21904077); 国家自然科学基金(22074074); 山东省高校优秀青年创新团队项目(2022KJC004); 山东省泰山学者计划(tstp20231227); 青岛市自然科学基金(23-2-1-175-zyyd-jch)

收起

A Turn-ON Near-Infrared Fluorescent Probe for the Detection of Dipeptidyl Peptidase IV Activity in Liver Cancers

  • Fei Zhang ,
  • Yu Mei ,
  • Xuefeng Ding ,
  • Zaifeng Li ,
  • Peng Zhang ,
  • Caifeng Ding
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  • Key Laboratory of Analytical Chemistry for Life Science in Universities of Shandong, Shandong Key Laboratory of Biochemical Analysis, Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science (Ministry of Education), College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, Shandong 266042
*Corresponding authors. E-mail:;
;

Received date: 2024-04-19

  Revised date: 2024-05-20

  Online published: 2024-06-13

Supported by

National Natural Science Foundation of China(21904077); National Natural Science Foundation of China(22074074); Youth Innovation Team Development Program of Shandong Higher Education Institutions(2022KJC004); Taishan Scholar Program of Shandong Province(tstp20231227); Natural Science Foundation of Qingdao City(23-2-1-175-zyyd-jch)

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摘要

二肽基肽酶(DPP-IV)作为一种癌细胞中过量表达的跨膜糖蛋白, 常被用于肿瘤早期检测的重要生物标志物. 开发了一种能够灵敏检测肝癌细胞中DPP-IV的开启型近红外荧光探针MB-DPP. 该探针以亚甲基蓝为荧光团, 以对氨基苯甲醇为连接臂, 通过脱水缩合反应键合甘氨酰-L-脯氨酸作为DPP-IV的特异性酶切位点, 从而实现DPP-IV触发的荧光“开启”反应, 探针MB-DPP与DPP-IV作用后在691 nm处发出强烈的近红外荧光. 光谱实验表明, 探针MB-DPP对DPP-VI表现出较高的选择性和检测灵敏度(检测限为1.12 ng/mL). 生物成像研究显示, MB-DPP不仅能实现了肝癌细胞内DPP-IV的活性荧光成像分析, 也可用于肝癌活体肿瘤内DPP-IV的活性成像. 因此探针MB-DPP的开发将有助于肝癌的早期诊断.

关键词： 二肽基肽酶; 近红外荧光探针; 亚甲基蓝; 肝癌; 活细胞成像; 活体成像

本文引用格式

张飞 , 梅煜 , 丁雪峰 , 李再峰 , 张鹏 , 丁彩凤 . 激活型近红外荧光探针用于肝癌中二肽基肽酶活性检测[J]. 有机化学, 2024 , 44(11) : 3417 -3426 . DOI: 10.6023/cjoc202404028

Abstract

Dipeptidyl peptidase IV (DPP-IV), a transmembrane glycoprotein overexpressed in cancer cells, is often used as an important biomarker for early detection of tumors. A near-infrared turn ON fluorescence probe (MB-DPP) was developed for the sensitively detection of DPP-IV in liver cancer cells. MB-DPP employs methylene blue as fluorophore and p-aminobenzyl alcohol as the connecting arm to bond glycyl-L-proline as the specific cleavage site of DPP-IV through dehydration condensation reaction, thereby achieving the fluorescence “turn on” reaction triggered by DPP-IV. Probe MB-DPP emits strong near-infrared fluorescence at 691 nm after the incubation with DPP-IV. Spectral experiments showed that MB-DPP exhibited high selectivity and detection sensitivity (with a detection limit of 1.12 ng/mL) for DPP-VI. Bio-imaging studies showed that MB-DPP could not only achieve fluorescence imaging analysis of DPP-IV activity in liver cancer cells, but also be used for imaging of DPP-IV in liver cancer tumors. Therefore, the development of probe MB-DPP will contribute to the early diagnosis of liver cancer.

Key words： dipeptidyl peptidase; near infrared fluorescent probe; methylene blue; liver cancer; living cell imaging; in vivo imaging

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