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A controllable self-localized imaging strategy capable of synchronous in situ tracking of local changes in intracellular bioactive small-molecules

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Abstract

In situ tracking and localization of ubiquitous bioactive small molecules (BSMs) within their native habitats is particularly challenging because of their low-molecular weight and widespread distribution properties. We report the proof of concept of a synchronous in situ imaging strategy, whereby the representative BSM amino-biothiols (ABs) mediate activation of the self-localizable probe HYPQS, thereby releasing insoluble emissive precipitates to afford holistic distribution information of ABs. Notably, three organelle-targetable ABs inhibitors were innovatively fabricated for directed clearance of ABs in particular organelles, providing a powerful aid for HYPQS to achieve programmed in situ tracking of ABs in different organelles “on demand”. Biological transmission electron microscopy images confirmed that this probe released insoluble emissive precipitates at the reaction sites, which is of primary importance for achieving synchronous in situ tracking of BSMs. Furthermore, the probe HYPQS was successfully applied to monitor the dynamic changes in the endogenous ABs pool during diverse cell events. This strategy opens a promising avenue for investigating the undiscovered functional mechanism of local BSMs in relevant biological processes.

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References

  1. Shen Y, Hu F, Min W. Annu Rev Biophys, 2019, 48: 347–369

    Article  CAS  PubMed  Google Scholar 

  2. Lee MH, Kim JS, Sessler JL. Chem Soc Rev, 2015, 44: 4185–4191

    Article  CAS  PubMed  Google Scholar 

  3. Gibson MI, Seyedsayamdost MR. ACS Cent Sci, 2018, 4: 437–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li K, Xu S, Xiong M, Huan SY, Yuan L, Zhang XB. Chem Soc Rev, 2021, 50: 11766–11784

    Article  CAS  PubMed  Google Scholar 

  5. Wu X, Wang R, Kwon N, Ma H, Yoon J. Chem Soc Rev, 2022, 51: 450–463

    Article  CAS  PubMed  Google Scholar 

  6. Wei L, Hu F, Shen Y, Chen Z, Yu Y, Lin CC, Wang MC, Min W. Nat Methods, 2014, 11: 410–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Contag CH, Moore A. Science, 2015, 350: 1270

    Article  Google Scholar 

  8. Vendrell M, Zhai D, Er JC, Chang YT. Chem Rev, 2012, 112: 4391–4420

    Article  CAS  PubMed  Google Scholar 

  9. Hong G, Antaris AL, Dai H. Nat Biomed Eng, 2017, 1: 0010

    Article  CAS  Google Scholar 

  10. Chan J, Dodani SC, Chang CJ. Nat Chem, 2012, 4: 973–984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ren TB, Zhang QL, Su D, Zhang XX, Yuan L, Zhang XB. Chem Sci, 2018, 9: 5461–5466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xu W, Zeng Z, Jiang JH, Chang YT, Yuan L. Angew Chem Int Ed, 2016, 55: 13658–13699

    Article  CAS  Google Scholar 

  13. Li H, Kim H, Zhang C, Zeng S, Chen Q, Jia L, Wang J, Peng X, Yoon J. Coord Chem Rev, 2022, 473: 214818

    Article  CAS  Google Scholar 

  14. Huang Z, Terpetschnig E, You W, Haugland RP. Anal Biochem, 1992, 207: 32–39

    Article  CAS  PubMed  Google Scholar 

  15. Li K, Hu XX, Liu HW, Xu S, Huan SY, Li JB, Deng TG, Zhang XB. Anal Chem, 2018, 90: 11680–11687

    Article  CAS  PubMed  Google Scholar 

  16. Liu HW, Li K, Hu XX, Zhu L, Rong Q, Liu Y, Zhang XB, Hasserodt J, Qu FL, Tan W. Angew Chem Int Ed, 2017, 56: 11788–11792

    Article  CAS  Google Scholar 

  17. Li K, Ren TB, Huan S, Yuan L, Zhang XB. J Am Chem Soc, 2021, 143: 21143–21160

    Article  CAS  PubMed  Google Scholar 

  18. Zhang X, Waibel M, Hasserodt J. Chem-Eur J, 2010, 16: 792–795

    Article  CAS  PubMed  Google Scholar 

  19. Li K, Lyu Y, Huang Y, Xu S, Liu HW, Chen L, Ren TB, Xiong M, Huan S, Yuan L, Zhang XB, Tan W. Proc Natl Acad Sci USA, 2021, 118: e2018033118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yin CX, Xiong KM, Huo FJ, Salamanca JC, Strongin RM. Angew Chem Int Ed, 2017, 56: 13188–13198

    Article  CAS  Google Scholar 

  21. Yin G, Niu T, Gan Y, Yu T, Yin P, Chen H, Zhang Y, Li H, Yao S. Angew Chem, 2018, 130: 5085–5088

    Article  Google Scholar 

  22. Yin C, Huo F, Zhang J, Martínez-Máñez R, Yang Y, Lv H, Li S. Chem Soc Rev, 2013, 42: 6032–6059

    Article  CAS  PubMed  Google Scholar 

  23. Huang Y, Zhang Y, Huo F, Chao J, Cheng F, Yin C. J Am Chem Soc, 2020, 142: 18706–18714

    Article  CAS  PubMed  Google Scholar 

  24. Chen X, Zhou Y, Peng X, Yoon J. Chem Soc Rev, 2010, 39: 2120–2135

    Article  CAS  PubMed  Google Scholar 

  25. Zhu J, Berisa M, Schwörer S, Qin W, Cross JR, Thompson CB. Cell Metab, 2019, 30: 865–876.e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Guo Z, Nam SW, Park S, Yoon J. Chem Sci, 2012, 3: 2760–2765

    Article  CAS  Google Scholar 

  27. Wei X, Jin T, Huang C, Jia N, Zhu W, Xu Y, Qian X. Coord Chem Rev, 2021, 429: 213621

    Article  CAS  Google Scholar 

  28. Niu W, Guo L, Li Y, Shuang S, Dong C, Wong MS. Anal Chem, 2016, 88: 1908–1914

    Article  CAS  PubMed  Google Scholar 

  29. Chen C, Zhou L, Liu W, Liu W. Anal Chem, 2018, 90: 6138–6143

    Article  CAS  PubMed  Google Scholar 

  30. Dong B, Lu Y, Zhang N, Song W, Lin W. Anal Chem, 2019, 91: 5513–5516

    Article  CAS  PubMed  Google Scholar 

  31. Gfeller D, Grosdidier A, Wirth M, Daina A, Michielin O, Zoete V. Nucl Acids Res, 2014, 42: W32–W38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wei H, Wu G, Tian X, Liu Z. Future Med Chem, 2018, 10: 2729–2744

    Article  CAS  PubMed  Google Scholar 

  33. Prescher JA, Bertozzi CR. Nat Chem Biol, 2005, 1: 13–21

    Article  CAS  PubMed  Google Scholar 

  34. Zheng Y, Hou P, Li Y, Sun J, Cui H, Zhang H, Chen S. Molecules, 2021, 26: 2337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang R, Yong J, Yuan J, Ping Xu Z. Coord Chem Rev, 2020, 408: 213182

    Article  CAS  Google Scholar 

  36. Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP, Orosz A, Zhang XQ, Stevenson TJ, Peshock RM, Leopold JA, Barry WH, Loscalzo J, Odelberg SJ, Benjamin IJ. Cell, 2007, 130: 427–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Badgley MA, Kremer DM, Maurer HC, DelGiorno KE, Lee HJ, Purohit V, Sagalovskiy IR, Ma A, Kapilian J, Firl CEM, Decker AR, Sastra SA, Palermo CF, Andrade LR, Sajjakulnukit P, Zhang L, Tolstyka ZP, Hirschhorn T, Lamb C, Liu T, Gu W, Seeley ES, Stone E, Georgiou G, Manor U, Iuga A, Wahl GM, Stockwell BR, Lyssiotis CA, Olive KP. Science, 2020, 368: 85–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li Z, Li Y, Yang Y, Gong Z, Zhu H, Qian Y. Anal Chim Acta, 2020, 1125: 66–75

    Article  CAS  PubMed  Google Scholar 

  39. Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S, Ingold I, Irmler M, Beckers J, Aichler M, Walch A, Prokisch H, Trümbach D, Mao G, Qu F, Bayir H, Füllekrug J, Scheel CH, Wurst W, Schick JA, Kagan VE, Angeli JPF, Conrad M. Nat Chem Biol, 2017, 13: 91–98

    Article  CAS  PubMed  Google Scholar 

  40. Hao S, Yu J, He W, Huang Q, Zhao Y, Liang B, Zhang S, Wen Z, Dong S, Rao J, Liao W, Shi M. Neoplasia, 2017, 19: 1022–1032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gao M, Yi J, Zhu J, Minikes AM, Monian P, Thompson CB, Jiang X. Mol Cell, 2019, 73: 354–363.e3

    Article  CAS  PubMed  Google Scholar 

  42. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison Iii B, Stockwell BR. Cell, 2012, 149: 1060–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, Goya Grocin A, Xavier da Silva TN, Panzilius E, Scheel CH, Mourão A, Buday K, Sato M, Wanninger J, Vignane T, Mohana V, Rehberg M, Flatley A, Schepers A, Kurz A, White D, Sauer M, Sattler M, Tate EW, Schmitz W, Schulze A, O’Donnell V, Proneth B, Popowicz GM, Pratt DA, Angeli JPF, Conrad M. Nature, 2019, 575: 693–698

    Article  CAS  PubMed  Google Scholar 

  44. Loomba R, Friedman SL, Shulman GI. Cell, 2021, 184: 2537–2564

    Article  CAS  PubMed  Google Scholar 

  45. Manickam P, Sudhakar R. Dig Dis Sci, 2013, 58: 1435–1437

    Article  PubMed  Google Scholar 

  46. Li W, Shen Y, Gong X, Zhang XB, Yuan L. Anal Chem, 2021, 93: 16673–16682

    Article  CAS  PubMed  Google Scholar 

  47. Li W, Wang L, Yin S, Lai H, Yuan L, Zhang X. Chem Sci, 2020, 11: 7991–7999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Li M, Xu C, Shi J, Ding J, Wan X, Chen D, Gao J, Li C, Zhang J, Lin Y, Tu Z, Kong X, Li Y, Yu C. Gut, 2018, 67: 2169–2180

  49. Robert K, Nehmé J, Bourdon E, Pivert G, Friguet B, Delcayre C, Delabar J–, Janel N. Gastroenterology, 2005, 128: 1405–1415

    Article  CAS  PubMed  Google Scholar 

  50. Sarna LK, Siow YL, OK. Can J Physiol Pharmacol, 2015, 93: 1–11

    Article  CAS  PubMed  Google Scholar 

  51. d’Emmanuele di Villa Bianca R, Sorrentino R, Maffia P, Mirone V, Imbimbo C, Fusco F, De Palma R, Ignarro LJ, Cirino G. Proc Natl Acad Sci USA, 2009, 106: 4513–4518

    Article  PubMed  PubMed Central  Google Scholar 

  52. Janošík M, Kery V, Gaustadnes M, Maclean KN, Kraus JP. Biochemistry, 2001, 40: 10625–10633

    Article  PubMed  Google Scholar 

  53. Kanuri G, Bergheim I. Int J Mol Sci, 2013, 14: 11963–11980

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (22234003, 22074036, 22204177), the Special Funds for the Construction of Innovative Provinces in Hunan Province (2021RC4021) and the Fundamental Research Funds for the Central Universities.

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Authors and Affiliations

  1. State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China

    Ke Li, Shuai Xu, Shuangyan Huan, Lin Yuan & Xiao-Bing Zhang

  2. College of Chemistry & Chemical Engineering, Central South University, Changsha, 410083, China

    Ke Li, Benhua Wang & Xiangzhi Song

  3. School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China

    Shuai Xu

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  1. Ke Li
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  2. Shuai Xu
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  3. Benhua Wang
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  4. Shuangyan Huan
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  5. Xiangzhi Song
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  6. Lin Yuan
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  7. Xiao-Bing Zhang
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Correspondence to Lin Yuan or Xiao-Bing Zhang.

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Supporting information The supporting information is available online at https://chem.scichina.com and https://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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11426_2023_1648_MOESM1_ESM.pdf

A Controllable Self-Localized Imaging Strategy Capable of Synchronous in Situ Tracking of Local Changes in Intracellular Bioactive Small-Molecules

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Li, K., Xu, S., Wang, B. et al. A controllable self-localized imaging strategy capable of synchronous in situ tracking of local changes in intracellular bioactive small-molecules. Sci. China Chem. 66, 2425–2434 (2023). https://doi.org/10.1007/s11426-023-1648-1

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