Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility
DNA strands containing a triazole linkage flanked on its 3′-side by an aminoethylphenoxazine nucleobase analogue (G-clamp) have been prepared by solid-phase synthesis followed by CuAAC-mediated click oligonucleotide ligation. The stability of the doubly modified DNA duplexes and DNA-RNA hybrids is g...
| Váldodahkkit: | , |
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| Materiálatiipa: | Journal article |
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Royal Society of Chemistry
2014
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| _version_ | 1826267320296669184 |
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| author | El-Sagheer, A Brown, T |
| author_facet | El-Sagheer, A Brown, T |
| author_sort | El-Sagheer, A |
| collection | OXFORD |
| description | DNA strands containing a triazole linkage flanked on its 3′-side by an aminoethylphenoxazine nucleobase analogue (G-clamp) have been prepared by solid-phase synthesis followed by CuAAC-mediated click oligonucleotide ligation. The stability of the doubly modified DNA duplexes and DNA-RNA hybrids is greatly increased, whereas a single base pair mismatch located at or adjacent to the modifications is strongly destabilising, making triazole G-clamp a potent mismatch/point mutation sensor. A DNA strand containing this unnatural combination was successfully amplified by PCR to produce unmodified copies of the original template, with deoxyguanosine inserted opposite to the G-clamp-triazole nucleotide analogue. This study shows for the first time that a polymerase enzyme can read through a combined backbone/nucleobase modification surprisingly well. These favourable properties suggest new applications for oligonucleotides containing the G-clamp triazole modification in biotechnology, nanotechnology, diagnostics and therapeutics. © 2013 The Royal Society of Chemistry. |
| first_indexed | 2024-03-06T20:52:22Z |
| format | Journal article |
| id | oxford-uuid:380686fb-d3a2-4de7-aa21-ae8af12d9928 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T20:52:22Z |
| publishDate | 2014 |
| publisher | Royal Society of Chemistry |
| record_format | dspace |
| spelling | oxford-uuid:380686fb-d3a2-4de7-aa21-ae8af12d99282022-03-26T13:47:33ZCombined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibilityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:380686fb-d3a2-4de7-aa21-ae8af12d9928Symplectic Elements at OxfordRoyal Society of Chemistry2014El-Sagheer, ABrown, TDNA strands containing a triazole linkage flanked on its 3′-side by an aminoethylphenoxazine nucleobase analogue (G-clamp) have been prepared by solid-phase synthesis followed by CuAAC-mediated click oligonucleotide ligation. The stability of the doubly modified DNA duplexes and DNA-RNA hybrids is greatly increased, whereas a single base pair mismatch located at or adjacent to the modifications is strongly destabilising, making triazole G-clamp a potent mismatch/point mutation sensor. A DNA strand containing this unnatural combination was successfully amplified by PCR to produce unmodified copies of the original template, with deoxyguanosine inserted opposite to the G-clamp-triazole nucleotide analogue. This study shows for the first time that a polymerase enzyme can read through a combined backbone/nucleobase modification surprisingly well. These favourable properties suggest new applications for oligonucleotides containing the G-clamp triazole modification in biotechnology, nanotechnology, diagnostics and therapeutics. © 2013 The Royal Society of Chemistry. |
| spellingShingle | El-Sagheer, A Brown, T Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility |
| title | Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility |
| title_full | Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility |
| title_fullStr | Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility |
| title_full_unstemmed | Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility |
| title_short | Combined nucleobase and backbone modifications enhance DNA duplex stability and preserve biocompatibility |
| title_sort | combined nucleobase and backbone modifications enhance dna duplex stability and preserve biocompatibility |
| work_keys_str_mv | AT elsagheera combinednucleobaseandbackbonemodificationsenhancednaduplexstabilityandpreservebiocompatibility AT brownt combinednucleobaseandbackbonemodificationsenhancednaduplexstabilityandpreservebiocompatibility |