Conformationally locked aryl C-nucleosides: synthesis of phosphoramidite monomers and incorporation into single-stranded DNA and LNA (locked nucleic acid)1

Babu, B. Ravindra; Prasad, Ashok K.; Trikha, S. K.; Thorup, Niels; Parmar, Virinder S.; Wengel, Jesper

doi:10.1039/b206626b

Cited by 22 publications

(4 citation statements)

References 29 publications

(35 reference statements)

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“…LNA‐type C ‐nucleosides have been synthesized by the groups of Obika [43] and Wengel [44] before. We chose the latter approach as a guideline for the synthesis of LNAzo‐phosphoramidites.…”

Section: Figurementioning

confidence: 99%

“…We chose the latter approach as a guideline for the synthesis of LNAzo‐phosphoramidites. Starting from aldehyde 1 , which can be synthesized over 11 steps from simple precursors as described in the literature [44, 45] (Figure 3), the azobenzene moiety can be introduced by nucleophilic attack as lithiated species, leading to separable ( S )‐ and ( R )‐diastereomers 2 and 3 , respectively. After Mitsunobu‐type cyclization to form anomers 4 and 5 , deprotection of the alcohol groups led to the free nucleosides 6 and 7 .…”

Section: Figurementioning

confidence: 99%

“…In this matter,l ocked azobenzene C-nucleosidesa re expectedt oy ield more promisingr esults.T he trans-azobenzene moiety has to be positioned in the stacking region and am igration of the intentionally bulky cis-photoisomer into the minor or major groove has to be prevented. [40] LNA-type C-nucleosides have been synthesized by the groups of Obika [43] and Wengel [44] before. We chose the latter approacha sag uideline for the synthesis of LNAzo-phosphoramidites.…”

mentioning

confidence: 99%

“…We chose the latter approacha sag uideline for the synthesis of LNAzo-phosphoramidites. Starting from aldehyde 1,w hich can be synthesized over 11 steps from simple precursors as described in the literature [44,45] (Figure 3), the azobenzene moiety can be introduced by nucleophilic attack as lithiated species, leading to separable (S)-and (R)-diastereomers 2 and 3,r espectively.A fter Mitsunobu-type cyclization to form anomers 4 and 5,d eprotection of the alcoholg roups led to the free nucleosides 6 and 7.T oi ncorporate LNAzo building blocks into oligonucleotides by solid-phase synthesis, phosphoramidites were prepared by tritylation( compounds 8 and 9)a nd successive phosphitylation (compounds 10 and 11). The DNAzo phosphoramidite used as reference in thiss tudy wass ynthesized as previously published.…”

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confidence: 99%

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Introducing LNAzo: More Rigidity for Improved Photocontrol of Oligonucleotide Hybridization**

Grebenovsky

Luma

Müller

et al. 2019

Chemistry A European J

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Oligonucleotide-based therapeutics have made rapid progress in clinical treatment of av ariety of disease indications. Since most therapeutic oligonucleotides serve more than just one functiona nd tend to have ap rolonged lifetime, spatio-temporal control of these functions would be desirable. Photoswitches like azobenzene have proven themselves as useful tools in this matter.U pon irradiation, the photoisomerization of the azobenzene moiety causes destabilization in adjacent base pairs, leading to ad ecreased hybridizationa ffinity.S ince the way the azobenzene is incorporated in the oligonucleotide is of utmosti mportance,w es ynthesized locked azobenzene Cnucleosides and compared their photocontrol capabilities to established azobenzene C-nucleosides in oligonucleotide test-sequences by meanso ff luorescence-, UV/Vis-, and CD-spectroscopy.Artificialc ontrol of biological functionr emains one of the most importantt opics of oligonucleotide chemistry.I nl iving organisms, oligonucleotide hybridization regulates the expression of genes and biosynthesis by revealing the encoded information only when desired. The simple base-pairingr ules led to many promisinga pplicationsin cell biology,p harmacology,o rn anotechnology. [1][2][3][4][5][6] For instance, oligonucleotide therapeutics against miRNA-34a play am ajor role in controlling cell proliferation. [7] However,m iRNA-34a is an important tumor suppressor and correspondinga ntimiRs have been shown to causes erious adversee ffects in off-target tissues in clinicalt rials [8] and have an in vivo half-life time of up to several weeks. [9] The need for ac onvenient method to add spatio-temporal control to therapeutic oligonucleotides led to many studies regardingt he distribution, cell uptake, and pharmacokinetics. [10][11][12] Ap ossible way of gainingc ontrol over these effects is the incorporationo fl ight-responsive elements. In contrast to most chemical stimuli, light does not pollute the system, is harmless for biological applicationsa nd can be applied with high spatio-temporalc ontrola nd dose-precision. [13][14][15] Several examples of photoactivatablea ntimiRs have been synthesized utilizing photocleavable protecting groups. [16,17] Unfortunately, activation of antimiRs with photocleavable protecting groups is an irreversible process;t herefore, adverse effects need to be taken into consideration. To harness the energy of light and translate it into ar eversible reaction, ar eversible system, which can be switched between different states,i sd esirable. Photoswitchesl ike spiropyrans, [18,19] hemithioindigos, [20] rhodopsins [21] or azobenzenes [22,23] can isomerize into different isoforms when irradiated with light of corresponding wavelength.Azobenzenes have ag reat potentialf or oligonucleotide applications.T hey are easy to synthesize, [24] can be custom tailored to the applications requirements, [25] and have already been used in numerous studies involving oligonucleotides. [22,26] Azobenzenes have two distinct photoisomers. The trans state azobenzene i...

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Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Introducing LNAzo: More Rigidity for Improved Photocontrol of Oligonucleotide Hybridization**

Grebenovsky

Luma

Müller

et al. 2019

Chemistry A European J

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Universal Base Analogues and their Applications to Biotechnology

Too

Loakes

2008

Modified Nucleosides

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Pyrenemethyl ara‐Uridine‐2′‐carbamate: A Strong Interstrand Excimer in the Major Groove of a DNA Duplex

et al. 2003

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The synthesis of new nucleoside derivatives, ara-uridine-2'-carbamates, and their incorporation into synthetic DNA oligomers is described. The modification directs ligands into the major groove of duplex DNA and somewhat destabilizes the duplexes of modified oligonucleotides with complementary DNA or RNA. In the case of pyrenemethyl carbamate modification in DNA-DNA duplexes, the destabilization is considerably reduced. The pyrenemethyl derivative also shows remarkable spectral properties: a "reversed" absorbance change for pyrene at 350 nm in the course of denaturation of the DNA duplex, as compared to the change seen in the nucleotide absorbance at 260 nm. This derivatization also causes pronounced sequence-dependent excimer formation in the major groove.

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Conformationally locked aryl C-nucleosides: synthesis of phosphoramidite monomers and incorporation into single-stranded DNA and LNA (locked nucleic acid)1

Cited by 22 publications

References 29 publications

Introducing LNAzo: More Rigidity for Improved Photocontrol of Oligonucleotide Hybridization**

Introducing LNAzo: More Rigidity for Improved Photocontrol of Oligonucleotide Hybridization**

Universal Base Analogues and their Applications to Biotechnology

Pyrenemethyl ara‐Uridine‐2′‐carbamate: A Strong Interstrand Excimer in the Major Groove of a DNA Duplex

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