| A nucleic acid dependent chemical photocatalysis in live human cells. | |
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MedLine Citation:
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PMID: 19894234 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Only two nucleic acid directed chemical reactions that are compatible with live cells have been reported to date. Neither of these processes generate toxic species from nontoxic starting materials. Reactions of the latter type could be applied as gene-specific drugs, for example, in the treatment of cancer. We report here the first example of a chemical reaction that generates a cytotoxic drug from a nontoxic prodrug in the presence of a specific endogeneous ribonucleic acid in live mammalian cells. In this case, the prodrug is triplet oxygen and the drug is singlet oxygen. The key component of this reaction is an inert molecule (InP-2'-OMe-RNA/Q-2'-OMe-RNA; P: photosensitizer; Q: quencher), which becomes an active photosensitizer (InP-2'-OMe-RNA) in the presence of single-stranded nucleic acid targets. Upon irradiation with red light, the photosensitizer produces over 6000 equivalents of toxic singlet oxygen per nucleic acid target. This reaction is highly sequence specific. To detect the generation of singlet oxygen in live cells, we prepared a membrane-permeable and water-soluble fluorescent scavenger, a derivative of 2,5-diphenylisobenzofurane. The scavenger decomposes upon reaction with singlet oxygen and this is manifested in a decrease in the fluorescence intensity. This effect can be conveniently monitored by flow cytometry. |
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Authors:
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Dumitru Arian; Emiliano Cl?; Kurt V Gothelf; Andriy Mokhir |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Chemistry (Weinheim an der Bergstrasse, Germany) Volume: 16 ISSN: 1521-3765 ISO Abbreviation: Chemistry Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-28 Completed Date: 2010-03-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9513783 Medline TA: Chemistry Country: Germany |
Other Details:
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Languages: eng Pagination: 288-95 Citation Subset: IM |
Affiliation:
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Anorganisch-Chemisches Institut, Ruprecht-Karls-Universit?t Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Base Sequence Catalysis Cell Line, Tumor Coloring Agents / chemistry Fluorescence Humans Nucleic Acids / chemistry* Photochemistry Photosensitizing Agents / chemistry* Porphyrins / chemistry Prodrugs / chemistry* RNA / chemistry*, metabolism Singlet Oxygen / chemistry* |
| Chemical | |
Reg. No./Substance:
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0/Coloring Agents; 0/Nucleic Acids; 0/Photosensitizing Agents; 0/Porphyrins; 0/Prodrugs; 17778-80-2/Singlet Oxygen; 63231-63-0/RNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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