Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors
Abstract Most activity-based molecular probes are designed to target enzymes that catalyze the breaking of chemical bonds and the conversion of a unimolecular substrate into bimolecular products. However, DNA topoisomerases are a class of enzymes that alter DNA topology without producing any molecul...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-021-01155-1 |
| _version_ | 1811306424509136896 |
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| author | Sai Ba Guangpeng Gao Tianhu Li Hao Zhang |
| author_facet | Sai Ba Guangpeng Gao Tianhu Li Hao Zhang |
| author_sort | Sai Ba |
| collection | DOAJ |
| description | Abstract Most activity-based molecular probes are designed to target enzymes that catalyze the breaking of chemical bonds and the conversion of a unimolecular substrate into bimolecular products. However, DNA topoisomerases are a class of enzymes that alter DNA topology without producing any molecular segments during catalysis, which hinders the development of practical methods for diagnosing these key biomarkers in living cells. Here, we established a new strategy for the effective sensing of the expression levels and catalytic activities of topoisomerases in cell-free systems and human cells. Using our newly designed biosensors, we tricked DNA topoisomerases within their catalytic cycles to switch on fluorescence and resume new rounds of catalysis. Considering that human topoisomerases have been widely recognized as biomarkers for multiple cancers and identified as promising targets for several anticancer drugs, we believe that these DNA-based biosensors and our design strategy would greatly benefit the future development of clinical tools for cancer diagnosis and treatment. Graphical Abstract |
| first_indexed | 2024-04-13T08:45:27Z |
| format | Article |
| id | doaj.art-5b6187f821af420d8a499c8293faa5cf |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T08:45:27Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-5b6187f821af420d8a499c8293faa5cf2022-12-22T02:53:44ZengBMCJournal of Nanobiotechnology1477-31552021-12-0119111410.1186/s12951-021-01155-1Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensorsSai Ba0Guangpeng Gao1Tianhu Li2Hao Zhang3School of Chemistry and Chemical Engineering, Northwestern Polytechnical UniversitySchool of Chemistry and Chemical Engineering, Northwestern Polytechnical UniversitySchool of Chemistry and Chemical Engineering, Northwestern Polytechnical UniversitySchool of Chemistry and Chemical Engineering, Northwestern Polytechnical UniversityAbstract Most activity-based molecular probes are designed to target enzymes that catalyze the breaking of chemical bonds and the conversion of a unimolecular substrate into bimolecular products. However, DNA topoisomerases are a class of enzymes that alter DNA topology without producing any molecular segments during catalysis, which hinders the development of practical methods for diagnosing these key biomarkers in living cells. Here, we established a new strategy for the effective sensing of the expression levels and catalytic activities of topoisomerases in cell-free systems and human cells. Using our newly designed biosensors, we tricked DNA topoisomerases within their catalytic cycles to switch on fluorescence and resume new rounds of catalysis. Considering that human topoisomerases have been widely recognized as biomarkers for multiple cancers and identified as promising targets for several anticancer drugs, we believe that these DNA-based biosensors and our design strategy would greatly benefit the future development of clinical tools for cancer diagnosis and treatment. Graphical Abstracthttps://doi.org/10.1186/s12951-021-01155-1DNA topoisomerasesCancer diagnosisEnzyme mechanismsDNA nanotechnologyDiagnostic probes |
| spellingShingle | Sai Ba Guangpeng Gao Tianhu Li Hao Zhang Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors Journal of Nanobiotechnology DNA topoisomerases Cancer diagnosis Enzyme mechanisms DNA nanotechnology Diagnostic probes |
| title | Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors |
| title_full | Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors |
| title_fullStr | Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors |
| title_full_unstemmed | Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors |
| title_short | Tricking enzymes in living cells: a mechanism-based strategy for design of DNA topoisomerase biosensors |
| title_sort | tricking enzymes in living cells a mechanism based strategy for design of dna topoisomerase biosensors |
| topic | DNA topoisomerases Cancer diagnosis Enzyme mechanisms DNA nanotechnology Diagnostic probes |
| url | https://doi.org/10.1186/s12951-021-01155-1 |
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