荧光多肽探针靶向检测细胞和斑马鱼中的钆离子

引用本文: 赵闯, 李佳楠, 孙秀霞, 肖建喜. 荧光多肽探针靶向检测细胞和斑马鱼中的钆离子[J]. 分析化学, 2022, 50(7): 1014-1021. doi: 10.19756/j.issn.0253-3820.221056 shu

Citation: ZHAO Chuang, LI Jia-Nan, SUN Xiu-Xia, XIAO Jian-Xi. A Novel Fluorescent Peptide Probe for Specific Detection of Gadolinium Ion(Ⅲ) in Cells and Zebrafish[J]. Chinese Journal of Analytical Chemistry, 2022, 50(7): 1014-1021. doi: 10.19756/j.issn.0253-3820.221056 shu

荧光多肽探针靶向检测细胞和斑马鱼中的钆离子

赵闯 ^1, ,
李佳楠 ^1, ,
孙秀霞 ^{2,
,} ,
肖建喜 ^{1,
,}

1.
兰州大学化学化工学院, 兰州 730000;
2.
兰州大学药学院, 兰州 730000

通讯作者: 孙秀霞,E-mail:sunxx@lzu.edu.cn; 肖建喜,E-mail:xiaojx@lzu.edu.cn

基金项目:
国家自然科学基金项目(Nos.22074057,21775059)资助。

摘要: 含钆造影剂作为临床应用最广泛的磁共振造影剂,在人体疾病的临床诊断和相关研究中发挥着非常重要的作用,而生物体内钆沉积被发现与肾源性系统性纤维化密切相关,并可能是多发性硬化、神经纤维瘤病、遗传性代谢紊乱等疾病的关键诱因。因此,实现生物体内游离的钆离子(Gd³⁺)高效检测对相关疾病的机理研究至关重要。本研究制备了一种新型荧光多肽探针PT (TPE-Glu-Glu-Glu-Pro-Gly-Glu-Glu-Glu),利用1-(4-羧基苯)-1,2,2-三苯乙烯(TPE)修饰的多肽探针PT,实现了溶液和体液中Gd³⁺的高效检测,并且不受其它常见金属离子的干扰;同时,Job工作曲线证明,荧光多肽探针PT与Gd³⁺以1∶3的方式结合,结合常数为2.34×10¹⁵ L³/mol³。在HEPES缓冲液和唾液样品中,随着Gd³⁺的加入,荧光多肽探针PT呈现"Turn-On"型响应模式,检出限分别为39和53 nmol/L,并成功用于小鼠成纤维细胞(L929细胞)和斑马鱼中Gd³⁺的靶向成像。此荧光多肽探针PT具有水溶性好、细胞毒性低等特性,可用于斑马鱼和L929细胞中Gd³⁺的高灵敏检测,在人体内残留Gd³⁺的分子诊断方面具有巨大的应用潜力。

关键词:

English

A Novel Fluorescent Peptide Probe for Specific Detection of Gadolinium Ion(Ⅲ) in Cells and Zebrafish

ZHAO Chuang ^1, ,
LI Jia-Nan ^1, ,
SUN Xiu-Xia ^{2,
,} ,
XIAO Jian-Xi ^{1,
,}

1.
College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China;
2.
School of Pharmacy, Lanzhou University, Lanzhou 730000, China

Corresponding author: SUN Xiu-Xia, ; XIAO Jian-Xi,

Received Date: 28 January 2022
Revised Date: 24 April 2022
Fund Project:
Supported by the National Natural Science Foundation of China (Nos.22074057, 21775059).

Abstract: As the most widely used magnetic resonance imaging contrast in clinical applications, gadolinium-based contrast agents play an important role in the clinical diagnosis and related research, while gadolinium deposition has been found to be closely related to nephrogenic systemic fibrosis and may cause multiple sclerosis, neurofibromatosis, inborn error of metabolism and other diseases. Therefore, the development of efficient assays for free Gd³⁺ is critical for the mechanistic study of these diseases. In this work, the fluorescent peptide probe PT consisted of (TPE-Glu-Glu-Glu-Pro-Gly-Glu-Glu-Glu) sequences was reported. The results showed that the efficient detection of Gd³⁺ in solution and biological fluids using the TPE-modified peptide probe PT without interferences of other metal ions was achieved. Meanwhile, the Job's analysis result indicated that the probe PT and Gd³⁺ formed a 1:3 complex and recovered its fluorescence, with a binding constant of 2.34×10¹⁵ L³/mol³. It was demonstrated that the fluorescent peptide probe PT provided a "Turn-On" sensing mode for Gd³⁺ with detection limits of 39 and 53 nmol/L in HEPES buffer solution and saliva samples. The probe PT was successfully used for imaging of Gd³⁺ in L929 cells and zebrafish. Notably, the newly developed fluorescent peptide probe PT had extraordinary features such as highly water solubility, low biotoxicity and high specificity for Gd³⁺ in zebrafish and L929 cells, which showed great potential in the molecular diagnosis of the concentration of residual Gd³⁺ in human body.

Key words:

1. [1]
  JIANG Shang-Da. Univ. Chem., 2019, 34(12):73-78.蒋尚达.大学化学, 2019, 34(12):73-78.
2. [2]
  WANG Qi-Rong, LI Xin-Fang, YANG Feng. Acad. J. Sec. Mil. Med. Univ., 2018, 39(11):1255-1258.王骐榕,李新方,杨峰.第二军医大学学报, 2018, 39(11):1255-1258.
3. [3]
  HUNT C H, HARTMAN R P, HESLEY G K. Am. J. Roentgenol., 2009, 193(4):1124-1127.HUNT C H, HARTMAN R P, HESLEY G K. Am. J. Roentgenol., 2009, 193(4):1124-1127.
4. [4]
  KHAIRINISA M A, TAKATSURU Y, AMANO I, ERDENE K, NAKAJIMA T, KAMEO S, KOYAMA H, TSUSHIMA Y, KOIBUCHI N. Invest. Radiol., 2018, 53(2):110-118.KHAIRINISA M A, TAKATSURU Y, AMANO I, ERDENE K, NAKAJIMA T, KAMEO S, KOYAMA H, TSUSHIMA Y, KOIBUCHI N. Invest. Radiol., 2018, 53(2):110-118.
5. [5]
  RADBRUCH A, HAASE R, KIESLICH P J, WEBERLING L D, KICKINGEREDER P, WICK W, SCHLEMMER H P, BENDSZUS M. Radiology, 2017, 282(3):699-707.RADBRUCH A, HAASE R, KIESLICH P J, WEBERLING L D, KICKINGEREDER P, WICK W, SCHLEMMER H P, BENDSZUS M. Radiology, 2017, 282(3):699-707.
6. [6]
  DUDEV T, LIM C. Chem. Rev., 2014, 114(1):538-556.DUDEV T, LIM C. Chem. Rev., 2014, 114(1):538-556.
7. [7]
  GONZALEZ-VERA J A. Chem. Soc. Rev., 2012, 41(5):1652-1664.GONZALEZ-VERA J A. Chem. Soc. Rev., 2012, 41(5):1652-1664.
8. [8]
  MEHTA P K, JEON J Y, RYU K, PARK S H, LEE K H. J. Hazard. Mater., 2022, 427:128161.MEHTA P K, JEON J Y, RYU K, PARK S H, LEE K H. J. Hazard. Mater., 2022, 427:128161.
9. [9]
  PAZOS E, VAZQUEZ O, MASCARENAS J L, VAZQUEZ M E. Chem. Soc. Rev., 2009, 38(12):3348-3359.PAZOS E, VAZQUEZ O, MASCARENAS J L, VAZQUEZ M E. Chem. Soc. Rev., 2009, 38(12):3348-3359.
10. [10]
  ZENG Rui-Di, YANG Tong, CHEN Jia-Hui, WANG Dan-Dan, ZHOU Xiao-Shun, SHAO Yong. Chin. J. Anal. Chem., 2021, 49(6):992-998.曾瑞迪,杨通,陈佳汇,王丹丹,周小顺,邵勇.分析化学, 2021, 49(6):992-998.
11. [11]
  KIM J M, LOHANI C R, NEUPANE L N, CHOI Y, LEE K H. Chem. Commun., 2012, 48(24):3012-3014.KIM J M, LOHANI C R, NEUPANE L N, CHOI Y, LEE K H. Chem. Commun., 2012, 48(24):3012-3014.
12. [12]
  HIRAYAMA T, TAKI M, AKAOKA K, YAMAMOTO Y. Bioorg. Med. Chem. Lett., 2012, 22(24):7410-7413.HIRAYAMA T, TAKI M, AKAOKA K, YAMAMOTO Y. Bioorg. Med. Chem. Lett., 2012, 22(24):7410-7413.
13. [13]
  LI Y X, ZHANG Y L, WANG M, WANG D J, CHEN K, LIN P C, GE Y S, LIU W S, WU J. J. Hazard. Mater., 2021, 415:125712.LI Y X, ZHANG Y L, WANG M, WANG D J, CHEN K, LIN P C, GE Y S, LIU W S, WU J. J. Hazard. Mater., 2021, 415:125712.
14. [14]
  HU Y, QUAN S Q, ZHAO C, LI J N, SUN X X, XIAO J X. New J. Chem., 2022, 46:7663-7668.HU Y, QUAN S Q, ZHAO C, LI J N, SUN X X, XIAO J X. New J. Chem., 2022, 46:7663-7668.
15. [15]
  HU Yue, QUAN Si-Qi, LI Jia-Nan, SUN Xiu-Xia, XIAO Jian-Xi. Sci. Sin. Chim., 2022, 52(1):117-124.胡悦,权思齐,李佳楠,孙秀霞,肖建喜.中国科学:化学, 2022, 52(1):117-124.
16. [16]
  BENESI H A, HILDBRAND J H. J. Am. Chem. Soc., 1949, 71:2703-2707.BENESI H A, HILDBRAND J H. J. Am. Chem. Soc., 1949, 71:2703-2707.
17. [17]
  KUNTZ I D, GASPARRO F P, JOHNSTON M D, TAYLOR R P. J. Am. Chem. Soc., 1968, 90(18):4778-4781.KUNTZ I D, GASPARRO F P, JOHNSTON M D, TAYLOR R P. J. Am. Chem. Soc., 1968, 90(18):4778-4781.
18. [18]
  GUI S L, HUANG Y Y, HU F, JIN Y L, ZHANG G X, ZHANG D Q, ZHAO R. Anal. Chem., 2018, 90(16):9708-9715.GUI S L, HUANG Y Y, HU F, JIN Y L, ZHANG G X, ZHANG D Q, ZHAO R. Anal. Chem., 2018, 90(16):9708-9715.
19. [19]
  WANG D, TANG B Z. Acc. Chem. Res., 2019, 52(9):2559-2570.WANG D, TANG B Z. Acc. Chem. Res., 2019, 52(9):2559-2570.

扫一扫看文章

计量

PDF下载量: 7
文章访问数: 772
HTML全文浏览量: 146

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

荧光多肽探针靶向检测细胞和斑马鱼中的钆离子

通讯作者: 孙秀霞,E-mail:sunxx@lzu.edu.cn; 肖建喜,E-mail:xiaojx@lzu.edu.cn

English

A Novel Fluorescent Peptide Probe for Specific Detection of Gadolinium Ion(Ⅲ) in Cells and Zebrafish

Corresponding author: SUN Xiu-Xia, ; XIAO Jian-Xi,

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

荧光多肽探针靶向检测细胞和斑马鱼中的钆离子

通讯作者: 孙秀霞,E-mail:sunxx@lzu.edu.cn; 肖建喜,E-mail:xiaojx@lzu.edu.cn

English

A Novel Fluorescent Peptide Probe for Specific Detection of Gadolinium Ion(Ⅲ) in Cells and Zebrafish

Corresponding author: SUN Xiu-Xia, ; XIAO Jian-Xi,

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

计量

文章相关

通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs