Charge-driven tripod somersault on DNA for ratiometric fluorescence imaging of small molecules in the nucleus
Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic aci...
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| Published in | Chemical science (Cambridge) Vol. 1; no. 43; pp. 153 - 164 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
CAMBRIDGE
Royal Soc Chemistry
21.11.2019
Royal Society of Chemistry |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2041-6520 2041-6539 |
| DOI | 10.1039/c9sc03594j |
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| Abstract | Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named "charge-driven tripod somersault on DNA", for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO
2
derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO
2
derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO
3
2−
/HSO
3
−
, a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe-DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both
in vitro
and
in vivo
ratiometric fluorescence imaging of the variations of endogenous SO
2
derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes.
We have developed a strategy "charge-driven tripod somersault on DNA" realizing both
in vitro
and
in vivo
ratiometric fluorescence imaging of the variations of endogenous SO
2
derivatives in the nucleus for the first time. |
|---|---|
| AbstractList | Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named “charge-driven tripod somersault on DNA”, for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO2 derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO2 derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO32−/HSO3−, a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe–DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO2 derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes. Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named “charge-driven tripod somersault on DNA”, for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO 2 derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO 2 derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO 3 2− /HSO 3 − , a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe–DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO 2 derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes. Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named "charge-driven tripod somersault on DNA", for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO /HSO , a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe-DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both and ratiometric fluorescence imaging of the variations of endogenous SO derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes. Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named "charge-driven tripod somersault on DNA", for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO2 derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO2 derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO3 2-/HSO3 -, a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe-DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO2 derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes.Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named "charge-driven tripod somersault on DNA", for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO2 derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO2 derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO3 2-/HSO3 -, a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe-DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO2 derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes. Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named "charge-driven tripod somersault on DNA", for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO 2 derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO 2 derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO 3 2− /HSO 3 − , a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe-DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO 2 derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes. We have developed a strategy "charge-driven tripod somersault on DNA" realizing both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO 2 derivatives in the nucleus for the first time. We have developed a strategy "charge-driven tripod somersault on DNA" realizing both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO 2 derivatives in the nucleus for the first time. Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named “charge-driven tripod somersault on DNA”, for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO 2 derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO 2 derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO 3 2– /HSO 3 – , a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe–DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO 2 derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes. Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their variations in the nucleus mainly due to the impermeable nuclear membrane and nucleic acid interference. Herein, we take advantage of the nucleic acid enriched environment in the nucleus to establish a strategy, named "charge-driven tripod somersault on DNA", for ratiometric fluorescence imaging of small bioactive molecules in the nucleus. Taking SO2 derivatives as a typical target analyte, a tripodal probe has been constructed by conjugating two DNA binding groups containing a SO2 derivative reaction site. Mechanism studies demonstrate that upon encountering and reacting with SO32-/HSO3-, a charge variation occurs at the responsive arm of the tripodal probe, triggering a tripod somersault on DNA, resulting in the conformational rearrangement of the DNA binding modes with DNA-modulated fluorescence change, which allows the second emission feature to emerge. In this strategy, probe-DNA binding is not influenced by RNA or non-specific protein association, thus making it ideal for tracing nucleus-localized analytes. The application of this strategy has realized both in vitro and in vivo ratiometric fluorescence imaging of the variations of endogenous SO2 derivatives in the nucleus for the first time, with high specificity and selectivity. Also, in theory, this strategy opens up a new avenue for the design of fluorescence probes for the nucleus-localized biological analytes. |
| Author | Xia, Wei Tan, Cai-Ping Wang, Kang-Nan Ji, Liang-Nian Zhao, Zi-Jian Liu, Liu-Yi Cao, Qian Mao, Zong-Wan Liu, Wenting Zhou, Dan-Jie |
| AuthorAffiliation | MOE Key Laboratory of Bioinorganic and Synthetic Chemistry Sun Yat-sen University School of Chemistry |
| AuthorAffiliation_xml | – sequence: 0 name: School of Chemistry – sequence: 0 name: Sun Yat-sen University – sequence: 0 name: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry – name: a MOE Key Laboratory of Bioinorganic and Synthetic Chemistry , School of Chemistry , Sun Yat-sen University , Guangzhou , 510275 , P. R. China . Email: caoqian3@mail.sysu.edu.cn ; Email: cesmzw@mail.sysu.edu.cn ; Fax: +86 20 8411 2245 |
| Author_xml | – sequence: 1 givenname: Kang-Nan surname: Wang fullname: Wang, Kang-Nan – sequence: 2 givenname: Qian surname: Cao fullname: Cao, Qian – sequence: 3 givenname: Liu-Yi surname: Liu fullname: Liu, Liu-Yi – sequence: 4 givenname: Zi-Jian surname: Zhao fullname: Zhao, Zi-Jian – sequence: 5 givenname: Wenting surname: Liu fullname: Liu, Wenting – sequence: 6 givenname: Dan-Jie surname: Zhou fullname: Zhou, Dan-Jie – sequence: 7 givenname: Cai-Ping surname: Tan fullname: Tan, Cai-Ping – sequence: 8 givenname: Wei surname: Xia fullname: Xia, Wei – sequence: 9 givenname: Liang-Nian surname: Ji fullname: Ji, Liang-Nian – sequence: 10 givenname: Zong-Wan surname: Mao fullname: Mao, Zong-Wan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32055359$$D View this record in MEDLINE/PubMed |
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| Keywords | SO2 DERIVATIVES OXIDATIVE STRESS LIVE-CELL HYDROGEN-PEROXIDE SENSORS BISULFITE PROBE SULFUR-DIOXIDE DERIVATIVES LIVING CELLS SULFIDE |
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| Snippet | Although fluorescence tracing of small bioactive molecules in living cells has been extensively studied, it is still a challenging task to detect their... We have developed a strategy "charge-driven tripod somersault on DNA" realizing both in vitro and in vivo ratiometric fluorescence imaging of the variations of... |
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| SubjectTerms | Binding Biocompatibility Biological activity Chemistry Chemistry, Multidisciplinary Crystallography Deoxyribonucleic acid Derivatives DNA Fluorescent indicators Imaging Physical Sciences Science & Technology Selectivity Strategy Titration Toxicity Tracing |
| Title | Charge-driven tripod somersault on DNA for ratiometric fluorescence imaging of small molecules in the nucleus |
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