At Tachment of Cholesterol to Amino-LNA: Synthesis and Hybridization Properties

Bryld, Torsten; Lomholt, Christian

doi:10.1080/15257770701549095

Cited by 13 publications

(10 citation statements)

References 4 publications

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“…It is particularly noteworthy that duplexes involving the doubly modified Q4 or S4 do not display transitions above 10 °C. Similar observations have been made with doubly cholesterol-modified 2′-amino-LNA . We hypothesize that interactions between the hydrophobic groups in single-stranded Q4 or S4 interfere with duplex formation.…”

Section: Resultssupporting

confidence: 84%

“…Similar observations have been made with doubly cholesterol-modified 2′-amino-LNA. 29 We hypothesize that interactions between the hydrophobic groups in single-stranded Q4 or S4 interfere with duplex formation. The fact that DNA duplexes with interstrand zipper arrangements of two Q monomers are rather thermostable supports this hypothesis (see Table S2, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

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Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

et al. 2014

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Oligonucleotides modified with conformationally restricted nucleotides such as locked nucleic acid (LNA) monomers are used extensively in molecular biology and medicinal chemistry to modulate gene expression at the RNA level. Major efforts have been devoted to the design of LNA derivatives that induce even higher binding affinity and specificity, greater enzymatic stability, and more desirable pharmacokinetic profiles. Most of this work has focused on modifications of LNA’s oxymethylene bridge. Here, we describe an alternative approach for modulation of the properties of LNA: i.e., through functionalization of LNA nucleobases. Twelve structurally diverse C5-functionalized LNA uridine (U) phosphoramidites were synthesized and incorporated into oligodeoxyribonucleotides (ONs), which were then characterized with respect to thermal denaturation, enzymatic stability, and fluorescence properties. ONs modified with monomers that are conjugated to small alkynes display significantly improved target affinity, binding specificity, and protection against 3′-exonucleases relative to regular LNA. In contrast, ONs modified with monomers that are conjugated to bulky hydrophobic alkynes display lower target affinity yet much greater 3′-exonuclease resistance. ONs modified with C5-fluorophore-functionalized LNA-U monomers enable fluorescent discrimination of targets with single nucleotide polymorphisms (SNPs). In concert, these properties render C5-functionalized LNA as a promising class of building blocks for RNA-targeting applications and nucleic acid diagnostics.

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Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

et al. 2014

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“…Different approaches have been investigated for preparing hydrophobic phosphoramidite building blocks including 2 0 -derivatized uridine, 4,29 derivatized heterocyclic bases, [44][45][46] and a thymine amino-LNA monomer. 47 Recently our group has reported an efficient and versatile access to a series of antagomir analogues. We described the synthesis of a 2 0 -lipid-amido uridine phosphoramidite building block via a Staudinger-Vilarrasa reaction.…”

Section: Philippe Barthe´le´mymentioning

confidence: 99%

Hybrid lipid oligonucleotide conjugates: synthesis, self-assemblies and biomedical applications

et al. 2011

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“…The 2´-amino-LNA provides a convenient chemical handle to which other groups can be conjugated, while at the same time maintaining the conformational properties associated with bridged nts (129). Examples of functional groups attached to LNA ONs include moieties introducing a positive charge for enhanced duplex and triplex stability (130,131), and cholesterol for increased efficiency of a miR knock down probe (132). Data suggest that 2´-amino-LNA seems to destabilize triplexes.…”

Section: Locked Nucleic Acidsmentioning

confidence: 99%

Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs

Gissberg

Zaghloul

Lundin

et al. 2016

Nucleic Acid Therapeutics

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AS1411 is a g-quadruplex-forming aptamer capable of selectively entering cancer cells by nucleolin receptor-mediated uptake. In this study, we investigated the cell internalization properties and plasticity of AS1411 carrying different locked nucleic acid-containing cargo oligonucleotides (ONs) for delivery into A549 and U2OS cells. We found that internalization efficiency is highly governed by ON cargo chemistry and composition since the inherent antitumor properties of AS1411 were lost when attached to a nontoxic ON, noTox. However, a toxic ON, Tox, demonstrated potent cytotoxicity after aptamer-mediated uptake in A549 cells. We also examined the effect of unlocked nucleic acid (UNA) modifications in the loop region of the aptamer, and how the cargo ONs and UNA incorporation affect the secondary structure of AS1411, in the presence or absence of two novel ellipticine derivatives. These findings add new insights to the design and future applications of aptamer-guided delivery of ON cargo to cancer cells.

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At Tachment of Cholesterol to Amino-LNA: Synthesis and Hybridization Properties

Abstract: Here, we present our synthesis of amino-LNA with a C6-linker and hybridization studies of these. A cholesterol moiety was attached at the end of the C6-linker. This resulted in drastic drops against DNA of the modified oligonucleotide.

Cited by 13 publications

References 4 publications

Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

Synthesis and Biophysical Properties of C5-Functionalized LNA (Locked Nucleic Acid)

Hybrid lipid oligonucleotide conjugates: synthesis, self-assemblies and biomedical applications

Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs

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