Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins
Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA) intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA) including siRNA, spliceosomal RNAs, tRNA,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/16/9/21392 |
| _version_ | 1811334738336546816 |
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| author | Gayani N. P. Dedduwa-Mudalige Christine S. Chow |
| author_facet | Gayani N. P. Dedduwa-Mudalige Christine S. Chow |
| author_sort | Gayani N. P. Dedduwa-Mudalige |
| collection | DOAJ |
| description | Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA) intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA) including siRNA, spliceosomal RNAs, tRNA, and rRNA. All of these RNAs play vital roles in the cell, such as catalysis of protein synthesis by rRNA, and therefore serve as potential drug targets. This work focused on platination of two highly conserved RNA hairpins from E. coli ribosomes, namely pseudouridine-modified helix 69 from 23S rRNA and the 790 loop of helix 24 from 16S rRNA. RNase T1 probing, MALDI mass spectrometry, and dimethyl sulfate mapping revealed platination at GpG sites. Chemical probing results also showed platination-induced RNA structural changes. These findings reveal solvent and structural accessibility of sites within bacterial RNA secondary structures that are functionally significant and therefore viable targets for cisplatin as well as other classes of small molecules. Identifying target preferences at the nucleotide level, as well as determining cisplatin-induced RNA conformational changes, is important for the design of more potent drug molecules. Furthermore, the knowledge gained through studies of RNA-targeting by cisplatin is applicable to a broad range of organisms from bacteria to human. |
| first_indexed | 2024-04-13T17:13:49Z |
| format | Article |
| id | doaj.art-563733c6c04f41e1a0acc35346468c82 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T17:13:49Z |
| publishDate | 2015-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-563733c6c04f41e1a0acc35346468c822022-12-22T02:38:12ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-09-01169213922140910.3390/ijms160921392ijms160921392Cisplatin Targeting of Bacterial Ribosomal RNA HairpinsGayani N. P. Dedduwa-Mudalige0Christine S. Chow1Department of Chemistry, Wayne State University, Detroit, MI 48202, USADepartment of Chemistry, Wayne State University, Detroit, MI 48202, USACisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA) intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA) including siRNA, spliceosomal RNAs, tRNA, and rRNA. All of these RNAs play vital roles in the cell, such as catalysis of protein synthesis by rRNA, and therefore serve as potential drug targets. This work focused on platination of two highly conserved RNA hairpins from E. coli ribosomes, namely pseudouridine-modified helix 69 from 23S rRNA and the 790 loop of helix 24 from 16S rRNA. RNase T1 probing, MALDI mass spectrometry, and dimethyl sulfate mapping revealed platination at GpG sites. Chemical probing results also showed platination-induced RNA structural changes. These findings reveal solvent and structural accessibility of sites within bacterial RNA secondary structures that are functionally significant and therefore viable targets for cisplatin as well as other classes of small molecules. Identifying target preferences at the nucleotide level, as well as determining cisplatin-induced RNA conformational changes, is important for the design of more potent drug molecules. Furthermore, the knowledge gained through studies of RNA-targeting by cisplatin is applicable to a broad range of organisms from bacteria to human.http://www.mdpi.com/1422-0067/16/9/21392cisplatinribosomal RNAhelix 69helix 24 |
| spellingShingle | Gayani N. P. Dedduwa-Mudalige Christine S. Chow Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins International Journal of Molecular Sciences cisplatin ribosomal RNA helix 69 helix 24 |
| title | Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins |
| title_full | Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins |
| title_fullStr | Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins |
| title_full_unstemmed | Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins |
| title_short | Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins |
| title_sort | cisplatin targeting of bacterial ribosomal rna hairpins |
| topic | cisplatin ribosomal RNA helix 69 helix 24 |
| url | http://www.mdpi.com/1422-0067/16/9/21392 |
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