Photophysical studies and submicron ring formation of morpholino U-nucleoside monomers

Paul, Subhojit; Jana, Santanu; Bhadra, Jhuma; Sinha, Surajit

doi:10.1039/c3cc45082a

Cited by 4 publications

(4 citation statements)

References 29 publications

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“…Fast isomer Slow isomer ESI+ (m/z) NH 3 10.37 (13) CH 3 NH 2 9.97 (11) Et 2 NH 9.49 (15) 8.03 (17) 6.92 (19) 2.14 (21) 8.89 (23) 8.76 (25) 6.75 (28) NH 2 8.49 (30) 9.32 (24) 8.59 (26) 10.43 (14) 10.28 (12) 10.15 (16) 8.56 (18) 7.39 (20) 2.62 (22) 903. 64 We also note that because this chemistry is orthogonal to other methods of DNA modification such as copper activated click reactions 18 or palladium catalyzed Stille couplings 19 , it opens avenues for labelling DNA with multiple functional groups and fluorophores.…”

Section: Nhr'r''mentioning

confidence: 99%

“…Chemically modified oligodeoxynucleotides (ODNs) − are used for applications in diagnostics, biomedical research, therapeutics, forensics, and material sciences. − For therapeutic applications, the modifications are introduced to confer properties such as enhanced nuclease stability, improved pharmacokinetics, stronger and more selective binding to complementary DNA/RNA, and improved cellular uptake. On the other hand, the use of DNA-based sensors, nanomaterials, diagnostic tools, and catalysts requires the attachment of labels such as fluorophores, quenchers, metal complexes, and electron paramagnetic resonance (EPR) labels …”

Section: Introductionmentioning

confidence: 99%

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Oxidative Substitution of Boranephosphonate Diesters as a Route to Post-synthetically Modified DNA

et al. 2015

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The introduction of modifications into oligonucleotides is important for a large number of applications in the nucleic acids field. However, the method of solid-phase DNA synthesis presents significant challenges for incorporating many useful modifications that are unstable to the conditions for preparing synthetic DNA. Here we report that boranephosphonate diesters undergo facile nucleophilic substitution in a stereospecific manner upon activation by iodine. We have subsequently used this reactivity to post-synthetically introduce modifications including azides and fluorophores into DNA by first synthesizing boranephosphonate-linked 2'-deoxyoligonucleotides and then treating these oligomers with iodine and various nucleophiles. In addition, we show that this reaction is an attractive method for preparing stereodefined phosphorus-modified oligonucleotides. We have also examined the mechanism of this reaction and show that it proceeds via an iodophosphate intermediate. Beyond nucleic acids synthesis, due to the ubiquity of phosphate derivatives in natural compounds and therapeutics, this stereospecific reaction has many potential applications in organophosphorus chemistry.

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Section: Nhr'r''mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxidative Substitution of Boranephosphonate Diesters as a Route to Post-synthetically Modified DNA

et al. 2015

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“…9 Therapeutic development of PMOs is currently underway in ongoing clinical trials for treatment of Duchenne muscular dystrophy (DMD) and against the infection and spread of the hemorrhagic filovirus Marburg. 10 Recent research has also demonstrated that PMOs may prove useful for studies in the nanotechnology 11 and surface hybridization 12 fields.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis of Phosphorodiamidate Morpholino Oligonucleotides and Their Chimeras Using Phosphoramidite Chemistry

Paul

Caruthers

2016

J. Am. Chem. Soc.

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Phosphorodiamidate morpholinos (PMOs) and PMO-DNA chimeras have been prepared on DNA synthesizers using phosphoramidite chemistry. This was possible by first generating boranephosphoroamidate morpholino internucleotide linkages followed by oxidative substitution with four different amines: N,N-dimethylamine, N-methylamine, ammonia, and morpholine. When compared to a natural DNA duplex, the amino modified PMO was found to have a higher melting temperature with either complementary DNA or RNA, whereas the remaining PMO analogues having morpholino, dimethylamino, or N-methylamino phosphorodiamidate linkages had melting temperatures that were either comparable or reduced. Additionally the N,N-dimethylamino PMO-DNA chimeras were found to stimulate RNaseH1 activity. Treatment of HeLa cells with fluorescently labeled PMO chimeras demonstrated that these analogues were efficiently taken up by cells in the presence of a lipid transfection reagent. Because of the simplistic synthesis procedures, various PMO analogues are now readily available and should therefore open new pathways for research into the antisense, diagnostic, and nanotechnology oligonucleotide fields.

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“…Chemically modified oligodeoxynucleotides − (ODNs) are used for applications in diagnostics, biomedical research, therapeutics, forensics, and material sciences. − For therapeutic applications, the modifications are introduced to confer properties such as enhanced nuclease stability, improved pharmacokinetics, stronger and more selective binding to complementary DNA/RNA, and improved cellular uptake . To date a large number of ODNs have been tested for biological activity with encouraging results that have stimulated much activity in this area.…”

Section: Introductionmentioning

confidence: 99%

Solid-Phase Synthesis, Hybridizing Ability, Uptake, and Nuclease Resistant Profiles of Position-Selective Cationic and Hydrophobic Phosphotriester Oligonucleotides

Monfregola

Caruthers

2015

J. Org. Chem.

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Analogues of oligonucleotides and mononucleotides with hydrophobic and/or cationic phophotriester functionalities often generate an improvement in target affinity and cellular uptake. Here we report the synthesis of phosphotriester oligodeoxyribonucleotides (ODNs) that are stable to the conditions used for their preparation. The method has been demonstrated by introducing phosphoramidite synthons where N-benzyloxycarbonyl (Z) protected amino alcohols replace the cyanoethyl group. After synthesis these ODNs were found to be stable to the condition required to remove base labile protecting groups and the ODNs from the solid support. Moreover the use of 1-(4,4-dimethyl-2, 6-dioxocyclohex-1-ylidene) ethyl (Dde) in place of Z protection on the amino alcohol has allowed us to introduce cationic aminoethyl phosphotriester modifications into ODNs. Melting temperatures of duplexes containing cationic or hydrophobic Z modified ODNs indicate that the backbone-phosphotriester modifications minimally affect duplex stability. Nuclease stability assays demonstrate that these phosphotriesters are resistant toward 5'- and 3'-exonucleases. Fluorescently labeled 23-mer ODNs modified with four cationic or hydrophobic Z phosphotriester linkages show efficient cellular uptake during passive transfection in HeLa and Jurkat cells.

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Photophysical studies and submicron ring formation of morpholino U-nucleoside monomers

Cited by 4 publications

References 29 publications

Oxidative Substitution of Boranephosphonate Diesters as a Route to Post-synthetically Modified DNA

Oxidative Substitution of Boranephosphonate Diesters as a Route to Post-synthetically Modified DNA

Synthesis of Phosphorodiamidate Morpholino Oligonucleotides and Their Chimeras Using Phosphoramidite Chemistry

Solid-Phase Synthesis, Hybridizing Ability, Uptake, and Nuclease Resistant Profiles of Position-Selective Cationic and Hydrophobic Phosphotriester Oligonucleotides

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