Near-infrared fluorogenic receptor for selective detection of cysteine in blood serum and living cells

Abstract

A novel near-infrared fluorescent probe, namely propane-2,2-diylbis(2-((E)-2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)-4,1-phenylene) diacrylate (BTA), was synthesized for selective detection of cysteine over other biologically significant amino acids. Upon addition of cysteine, the probe BTA displays a dramatic increase in fluorescence intensity at 715 nm along with a fast response time (4 min). The limit of detection (LOD) was calculated as 0.12 μM. In addition, the synthesized probe BTA was effectively utilized for the recognition of cysteine in blood serum and living cells.

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References

  1. 1.

    Wood ZA, Schroder E, Harris JR. Poole LB. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci 2003;28:32–40.

  2. 2.

    Suzuki Y, Suda K, Matsuyama Y, Era S, Soejima A. Close relationship between redox state of human serum albumin and serum cysteine levels in non-diabetic CKD patients with various degrees of renal function. Clin Nephrol. 2014;82:320–5.

    CAS  Article  Google Scholar 

  3. 3.

    Zhang SY, Ong CN, Shen HM. Involvement of proapoptotic Bcl-2 family members in parthenolide-induced mitochondrial dysfunction and apoptosis. Cancer Lett. 2004;211:175–88.

    CAS  Article  Google Scholar 

  4. 4.

    Duke RM, Veale EB, Pfeffer FM, Kruger PE, Gunnlaugsson T. Colorimetric and fluorescent anion sensors: an overview of recent developments in the use of 1,8-naphthalimide-based chemosensors. Chem Soc Rev. 2010;39:3936–53.

    CAS  Article  Google Scholar 

  5. 5.

    Zhang S, Ong CN, Shen HM. Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells. Cancer Lett. 2004;208:143–53.

    CAS  Article  Google Scholar 

  6. 6.

    Miller JW, Beresford SAA, Neuhouser NL, Cheng TY, Song DX, Brown EC, et al. Homocysteine, cysteine, and risk of incident colorectal Cancer in the Women’s health initiative observational cohort. Am J Clin Nutr. 2013;97:827–34.

    CAS  Article  Google Scholar 

  7. 7.

    Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346:476–83.

    CAS  Article  Google Scholar 

  8. 8.

    Kirthika Rani B, Abraham JS. A novel pyrene based fluorescent probe for selective detection of cysteine in presence of other bio-thiols in living cells. Biosens Bioelectron. 2016;83:237–42.

    Article  Google Scholar 

  9. 9.

    Li Y. A ratiometric fluorescent chemosensor for the detection of cysteine in aqueous solution at neutral pH. Luminescence. 2017;32:1385–90.

    CAS  Article  Google Scholar 

  10. 10.

    Hou X, Li Z, Li B, Liu C, Xu Z. An “off-on” fluorescein-based colormetric and fluorescent probe for the detection of glutathione and cysteine over homocysteine and its application for cell imaging. Sens. Actuators B Chem. 2018;260:295–302.

    CAS  Article  Google Scholar 

  11. 11.

    Wang FF, Fan XY, Liu YJ, Gao T, Huang R, Jiang FL, et al. Design, synthesis, cell imaging, kinetics and thermodynamics of reaction-based turn-on fluorescent probes for the detection of biothiols. Dyes Pigmen. 2017;145:451–60.

    CAS  Article  Google Scholar 

  12. 12.

    Wang Q, Wei X, Li C, Xie Y. A novel p-aminophenylthio- and cyano-substituted BODIPY as a fluorescence turn-on probe for distinguishing cysteine and homocysteine from glutathione. Dyes Pigmen. 2018;148:212–8.

    CAS  Article  Google Scholar 

  13. 13.

    Wang J, Niu L, Huang J, Yan Z, Zhou X, Wang J. Thiazolyl substituted NBD as fluorescent probe for the detection of homocysteine and cysteine. Dyes Pigmen. 2018;158:151–6.

    CAS  Article  Google Scholar 

  14. 14.

    Nie L, Guo B, Gao C, Zhang S, Jing J, Zhang X. Specific and sensitive imaging of basal cysteine over homocysteine in living cells. RSC Adv. 2018;8:37410–6.

    CAS  Article  Google Scholar 

  15. 15.

    Xu G, Tang Y. Lin W. A multi-signal fluorescent probe for the discrimination of cysteine/homocysteine and glutathione and application in living cells and zebrafish. New J Chem 2018;42:12615–12620.

  16. 16.

    Chen K, Zhang M, Qi Y, Fan J, Ma X, Zhu H, et al. Imaging dynamic changes of intracellular cysteine pool that respond to the stimulation of external oxidative stress. Analyst. 2014;144:2320–6.

    Article  Google Scholar 

  17. 17.

    Gao S, Tang Y, Lin W. Development of a two-photon turn-on fluorescent probe for cysteine and its bio-imaging applications in living cells, tissues, and zebrafish. New J Chem. 2018;42:14075–8.

    CAS  Article  Google Scholar 

  18. 18.

    Dai X, Wu QH, Wang PC, Tian J, Xu Y, Wang SQ, et al. A simple and effective coumarin-based fluorescent probe for cysteine. Biosens Bioelectron. 2014;59:35–9.

    CAS  Article  Google Scholar 

  19. 19.

    Tang L, Xu D, Tian M, Yan X. A mitochondria-targetable far-red emissive fluorescence probe for highly selective detection of cysteine with a large stokes shift. J Lumin. 2019;208:502–8.

    CAS  Article  Google Scholar 

  20. 20.

    Feng S, Fang Y, Feng W, Xia Q, Feng G. A colorimetric and ratiometric fluorescent probe with enhanced near-infrared fluorescence for selective detection of cysteine and its application in living cells. Dyes Pigmen. 2017;146:103–11.

    CAS  Article  Google Scholar 

  21. 21.

    Dai X, Kong X, Lin W. A novel fluorescent probe with large stokes shift for two-photon imaging of biothiols in living cells, liver tissues and tumor tissues. Dyes Pigmn. 2017;142:306–14.

    CAS  Article  Google Scholar 

  22. 22.

    Guo X, Xia L, Huang J, Wang Y, Gu Y, Wang P. Novel dual-site fluorescent probe for monitoring cysteine and sulfite in living cells. RSC Adv. 2018;8:21047–53.

    CAS  Article  Google Scholar 

  23. 23.

    Li Y, Liu W, Zhang P, Zhang H, Wu J, Ge J, et al. A fluorescent probe for efficient discrimination of Cys, HCy and GSH based on different cascade reactions. Biosens Bioelectron. 2017;90:117–24.

    CAS  Article  Google Scholar 

  24. 24.

    Lindoy LF, Meehan GV, Svenstrup N. Mono-and diformylation of 4-substituted phenols: a new application of the duff reaction. Synthesis. 1998:1029–32.

  25. 25.

    Vidya B, Iniya M, Sivaraman G, Sumesh RV, Chellappa D. Diverse benzothiazole based chemodosimeters for the detection of cyanide in aqueous media and in HeLa cells. Sens Actuators B Chem. 2017;242:434–2.

    CAS  Article  Google Scholar 

  26. 26.

    Duan Z, Zhu Y, Yang Y, He Z, Liu J, Li P, et al. Fluorescent imaging for cysteine detection in vivo with high selectivity. ChemistryOpen. 2019;8:316–20.

    CAS  Article  Google Scholar 

  27. 27.

    Wang J, Li B, Zhao W, Zhang X, Luo X, Corkins ME, et al. Two-photon near infrared (NIR-NIR) fluorescent turn-on probe towards cysteine (Cys) and its imaging applications. ACS Sens. 2016;1:882–7.

    CAS  Article  Google Scholar 

  28. 28.

    Chen C, Zhou L, Liu W, Liu W. Coumarinocoumarin-based two-photon fluorescent cysteine biosensor for targeting lysosome. Anal Chem. 2018;90:6138–43.

    CAS  Article  Google Scholar 

  29. 29.

    Zhang W, Liu J, Yu Y, Han Q, Chen T, Shen J, et al. A novel near-infrared fluorescent probe for highly selective detection of cysteine and its application in living cells. Talanta. 2018;185:477–82.

    CAS  Article  Google Scholar 

Download references

Acknowledgments

One of the authors (A.G) thanks the Department of Science and Technology, Ministry of Science and Technology, Government of India, for a fellowship under the INSPIRE scheme (No. IF140098). The authors also express their sincere thanks to the Council of Scientific and Industrial Research (CSIR), New Delhi, India [Grant No. 01 (2907)/17/EMR-II] and University Grants Commission (UGC), India [SAP grant No. 540/20/DRS-I/2016(SAP-I)] for financial assistance.

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Conceptualization: Periasamy Viswanathamurthi; methodology: Asaithambi Gomathi; formal analysis and investigation: Asaithambi Gomathi and Jebiti Haribabu; writing—original draft preparation: Asaithambi Gomathi; writing—review and editing: Periasamy Viswanathamurthi; funding acquisition: Periasamy Viswanathamurthi; resources: Periasamy Viswanathamurthi; supervision: Periasamy Viswanathamurthi.

Corresponding author

Correspondence to Viswanathamurthi Periasamy.

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The biological studies have been approved by the Human Ethics Committee (Government Mohan Kumaramangalam Medical College and Hospital/4341/IEC/2019-306) and have been performed in accordance with the ethical standards.

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The authors declare that they have no conflict of interest.

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Asaithambi, G., Periasamy, V. & Jebiti, H. Near-infrared fluorogenic receptor for selective detection of cysteine in blood serum and living cells. Anal Bioanal Chem 413, 1817–1826 (2021). https://doi.org/10.1007/s00216-020-03149-8

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Keywords

  • NIR probe
  • Cysteine detection
  • Real sample analysis
  • Living cells