Locked nucleic acid (LNA) enhances binding affinity of triazole-linked DNA towards RNA

Kumar, Pawan; El‐Sagheer, Afaf H.; Truong, Lynda; Brown, Tom

doi:10.1039/c7cc05159j

Cited by 27 publications

(43 citation statements)

References 28 publications

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“…It is also possible that such oligonucleotide analogues will have different toxicological properties than LNA because it is not possible for any of the LNA–triazole dimers to be degraded into LNA nucleotides, so they cannot enter the mononucleotide triphosphate pool and therefore they cannot be incorporated into genomic DNA or RNA. The results presented here and previously 16 suggest that, in addition to potential therapeutic applications, modified t-LNAs could find uses in imaging, diagnostics, and nontherapeutic siRNA applications.…”

Section: Discussionsupporting

confidence: 63%

“…To a solution of nucleoside 1 ( 16 ) (0.74 g, 1.21 mmol) in DMF (5 mL) was added benzoic anhydride (0.41 g, 1.81 mmol). The reaction mixture was stirred at room temperature for 18 h. The solvent was removed and the residue was taken up in EtOAc (100 mL), washed with sat.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous study, we incorporated monomers W – Z into oligonucleotides by ligating together two short ONs, one with a 5′-azide group and the other with a 3′-propargyl group. 16 This approach was chosen for ease of ON synthesis. However, multiple incorporations of the triazole linkage into short ONs and the introduction of the linkage at the ends of ONs is not practical using this strategy.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Affinity for Complementary RNA and DNA, and Enzymatic Stability of Triazole-Linked Locked Nucleic Acids (t-LNAs)

et al. 2018

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Dinucleoside phosphoramidites containing a triazole internucleotide linkage flanked by locked nucleic acid (LNA) were synthesized and incorporated into oligonucleotides (ONs). ONs bearing both LNA and triazole at multiple sites were obtained and their biophysical properties including enzymatic stability and binding affinity for RNA and DNA targets were studied. t-LNAs with four incorporations of a dinucleoside monomer having LNA on either side of the triazole linkage bind to their RNA target with significantly higher affinity and greater specificity than unmodified oligonucleotides, and are remarkably stable to nuclease degradation. A similar but reduced effect on enzymatic stability and binding affinity was noted for LNA only on the 3′-side of the triazole linkage. Thus, by combining unnatural triazole linkages and LNA in one unit (t-LNA), we produced a promising class of ONs with reduced anionic charge and potential for antisense applications.

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Section: Discussionsupporting

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis, Affinity for Complementary RNA and DNA, and Enzymatic Stability of Triazole-Linked Locked Nucleic Acids (t-LNAs)

et al. 2018

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“…Notably, there are no reports to date of EPO polypeptides modified by the CuAAC reaction. As the 1,2,3-triazole ring is known to be resistant to enzymatic hydrolysis,32,33 conjugation of the peptide and carbohydrate moieties by CuAAC would render the neoglycosylated EPO less susceptible to enzymatic degradation, potentially prolonging biological activity in vivo . Furthermore, the ability to readily ‘click’ different oligosaccharides at different positions on the peptide backbone in a divergent manner should enable the synthesis of homogeneous neoglycosylated EPO analogues to provide further insight into the role of glycans on the bioactivity of EPO.…”

Section: Introductionmentioning

confidence: 99%

A synthetic approach to ‘click’ neoglycoprotein analogues of EPO employing one-pot native chemical ligation and CuAAC chemistry

et al. 2019

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“…AMOs and 2′-O-methoxyethyl are LNA anti-miRs (Kumar et al, 2017). Table 3 represents important instances of miRNA-reduction therapies.…”

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confidence: 99%

MicroRNA replacement therapy in cancer

Mollaei

Safaralizadeh

Rostami

2019

Journal Cellular Physiology

202

147

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Despite the recent progress in cancer management approaches, the mortality rate of cancer is still growing and there are lots of challenges in the clinics in terms of novel therapeutics. MicroRNAs (miRNA) are regulatory small noncoding RNAs and are already confirmed to have a great role in regulating gene expression level by targeting multiple molecules that affect cell physiology and disease development. Recently, miRNAs have been introduced as promising therapeutic targets for cancer treatment. Regulatory potential of tumor suppressor miRNAs, which enables regulation of entire signaling networks within the cells, makes them an interesting option for developing cancer therapeutics. In this regard, over recent decades, scientists have aimed at developing powerful and safe targeting approaches to restore these suppressive miRNAs in cancerous cells. The present review summarizes the function of miRNAs in tumor development and presents recent findings on how miRNAs have served as therapeutic agents against cancer, with a special focus on tumor suppressor miRNAs (mimics). Moreover, the latest investigations on the therapeutic strategies of miRNA delivery have been presented.

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Locked nucleic acid (LNA) enhances binding affinity of triazole-linked DNA towards RNA

Abstract: LNA improves the RNA-binding affinity and enzymatic stability of triazole-linked DNA.

Cited by 27 publications

References 28 publications

Synthesis, Affinity for Complementary RNA and DNA, and Enzymatic Stability of Triazole-Linked Locked Nucleic Acids (t-LNAs)

Synthesis, Affinity for Complementary RNA and DNA, and Enzymatic Stability of Triazole-Linked Locked Nucleic Acids (t-LNAs)

A synthetic approach to ‘click’ neoglycoprotein analogues of EPO employing one-pot native chemical ligation and CuAAC chemistry

MicroRNA replacement therapy in cancer

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