DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

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dc.citation.volume17
dc.contributor.authorSu Y
dc.contributor.authorBayarjargal M
dc.contributor.authorHale TK
dc.contributor.authorFilichev VV
dc.contributor.editorKumar P
dc.contributor.editorBrown T
dc.coverage.spatialGermany
dc.date.accessioned2023-12-15T01:10:34Z
dc.date.accessioned2024-07-25T06:51:45Z
dc.date.available2021-03-29
dc.date.available2023-12-15T01:10:34Z
dc.date.available2024-07-25T06:51:45Z
dc.date.issued2021-03-29
dc.description.abstractTwo phosphate modifications were introduced into the DNA backbone using the Staudinger reaction between the 3',5'-dinucleoside β-cyanoethyl phosphite triester formed during DNA synthesis and sulfonyl azides, 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide (N+ azide) or p-toluenesulfonyl (tosyl or Ts) azide, to provide either a zwitterionic phosphoramidate with N+ modification or a negatively charged phosphoramidate for Ts modification in the DNA sequence. The incorporation of these N+ and Ts modifications led to the formation of thermally stable parallel DNA triplexes, regardless of the number of modifications incorporated into the oligodeoxynucleotides (ONs). For both N+ and Ts-modified ONs, the antiparallel duplexes formed with complementary RNA were more stable than those formed with complementary DNA (except for ONs with modification in the middle of the sequence). Additionally, the incorporation of N+ modifications led to the formation of duplexes with a thermal stability that was less dependent on the ionic strength than native DNA duplexes. The thermodynamic analysis of the melting curves revealed that it is the reduction in unfavourable entropy, despite the decrease in favourable enthalpy, which is responsible for the stabilisation of duplexes with N+ modification. N+ONs also demonstrated greater resistance to nuclease digestion by snake venom phosphodiesterase I than the corresponding Ts-ONs. Cell uptake studies showed that Ts-ONs can enter the nucleus of mouse fibroblast NIH3T3 cells without any transfection reagent, whereas, N+ONs remain concentrated in vesicles within the cytoplasm. These results indicate that both N+ and Ts-modified ONs are promising for various in vivo applications.
dc.description.confidentialfalse
dc.edition.edition2021
dc.format.pagination749-761
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/33828619
dc.identifier.citationSu Y, Bayarjargal M, Hale TK, Filichev VV. (2021). DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies.. Beilstein J Org Chem. 17. (pp. 749-761).
dc.identifier.doi10.3762/bjoc.17.65
dc.identifier.eissn1860-5397
dc.identifier.elements-typejournal-article
dc.identifier.issn1860-5397
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/71048
dc.languageeng
dc.publisherBeilstein-Institut
dc.publisher.urihttps://www.beilstein-journals.org/bjoc/articles/17/65
dc.relation.isPartOfBeilstein J Org Chem
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectDNA
dc.subjectStaudinger reaction
dc.subjectcell uptake
dc.subjectcharge neutral modification
dc.subjectmodified phosphates
dc.titleDNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies
dc.typeJournal article
pubs.elements-id444236
pubs.organisational-groupOther
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