Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides : Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA. / Danielsen, Mathias B.; Christensen, Niels Johan; Jørgensen, Per T.; Jensen, Knud J.; Wengel, Jesper; Lou, Chenguang.

In: Chemistry: A European Journal, Vol. 27, No. 4, 2021, p. 1416-1422.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Danielsen, MB, Christensen, NJ, Jørgensen, PT, Jensen, KJ, Wengel, J & Lou, C 2021, 'Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA', Chemistry: A European Journal, vol. 27, no. 4, pp. 1416-1422. https://doi.org/10.1002/chem.202004495

APA

Danielsen, M. B., Christensen, N. J., Jørgensen, P. T., Jensen, K. J., Wengel, J., & Lou, C. (2021). Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA. Chemistry: A European Journal, 27(4), 1416-1422. https://doi.org/10.1002/chem.202004495

Vancouver

Danielsen MB, Christensen NJ, Jørgensen PT, Jensen KJ, Wengel J, Lou C. Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA. Chemistry: A European Journal. 2021;27(4):1416-1422. https://doi.org/10.1002/chem.202004495

Author

Danielsen, Mathias B. ; Christensen, Niels Johan ; Jørgensen, Per T. ; Jensen, Knud J. ; Wengel, Jesper ; Lou, Chenguang. / Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides : Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA. In: Chemistry: A European Journal. 2021 ; Vol. 27, No. 4. pp. 1416-1422.

Bibtex

@article{f48267bf4b1a4987847d8a389af4c93e,
title = "Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA",
abstract = "Attachment of cationic moieties to oligonucleotides (ONs) promises not only to increase the binding affinity of antisense ONs by reducing charge repulsion between the two negatively charged strands of a duplex, but also to augment their in vivo stability against nucleases. In this study, polyamine functionality was introduced into ONs by means of 2′-amino-LNA scaffolds. The resulting ONs exhibited efficient binding towards ssDNA, ssRNA and dsDNA targets, and the 2′-amino-LNA analogue carrying a triaminated linker showed the most pronounced duplex- and triplex-stabilizing effect. Molecular modelling revealed that favourable conformational and electrostatic effects led to salt-bridge formation between positively charged polyamine moieties and the Watson–Hoogsteen groove of the dsDNA targets, resulting in the observed triplex stabilization. All the investigated monomers showed increased resistance against 3′-nucleolytic digestion relative to the non-functionalized controls.",
author = "Danielsen, {Mathias B.} and Christensen, {Niels Johan} and J{\o}rgensen, {Per T.} and Jensen, {Knud J.} and Jesper Wengel and Chenguang Lou",
year = "2021",
doi = "10.1002/chem.202004495",
language = "English",
volume = "27",
pages = "1416--1422",
journal = "Chemistry: A European Journal",
issn = "0947-6539",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "4",

}

RIS

TY - JOUR

T1 - Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides

T2 - Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA

AU - Danielsen, Mathias B.

AU - Christensen, Niels Johan

AU - Jørgensen, Per T.

AU - Jensen, Knud J.

AU - Wengel, Jesper

AU - Lou, Chenguang

PY - 2021

Y1 - 2021

N2 - Attachment of cationic moieties to oligonucleotides (ONs) promises not only to increase the binding affinity of antisense ONs by reducing charge repulsion between the two negatively charged strands of a duplex, but also to augment their in vivo stability against nucleases. In this study, polyamine functionality was introduced into ONs by means of 2′-amino-LNA scaffolds. The resulting ONs exhibited efficient binding towards ssDNA, ssRNA and dsDNA targets, and the 2′-amino-LNA analogue carrying a triaminated linker showed the most pronounced duplex- and triplex-stabilizing effect. Molecular modelling revealed that favourable conformational and electrostatic effects led to salt-bridge formation between positively charged polyamine moieties and the Watson–Hoogsteen groove of the dsDNA targets, resulting in the observed triplex stabilization. All the investigated monomers showed increased resistance against 3′-nucleolytic digestion relative to the non-functionalized controls.

AB - Attachment of cationic moieties to oligonucleotides (ONs) promises not only to increase the binding affinity of antisense ONs by reducing charge repulsion between the two negatively charged strands of a duplex, but also to augment their in vivo stability against nucleases. In this study, polyamine functionality was introduced into ONs by means of 2′-amino-LNA scaffolds. The resulting ONs exhibited efficient binding towards ssDNA, ssRNA and dsDNA targets, and the 2′-amino-LNA analogue carrying a triaminated linker showed the most pronounced duplex- and triplex-stabilizing effect. Molecular modelling revealed that favourable conformational and electrostatic effects led to salt-bridge formation between positively charged polyamine moieties and the Watson–Hoogsteen groove of the dsDNA targets, resulting in the observed triplex stabilization. All the investigated monomers showed increased resistance against 3′-nucleolytic digestion relative to the non-functionalized controls.

U2 - 10.1002/chem.202004495

DO - 10.1002/chem.202004495

M3 - Journal article

C2 - 33073896

VL - 27

SP - 1416

EP - 1422

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

IS - 4

ER -

ID: 257921524