Pharmacology and Therapeutics, volume 217, pages 107649

G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects

C. Riccardi ^{1, 2}

Ettore Napolitano ³

Chiara Platella ³

Domenica Musumeci ³

Daniela Montesarchio ³

Hide authors affiliations Show authors affiliations: 3 affiliations

Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania Luigi Vanvitelli, via Sergio Pansini 5, I-80131 Naples, Italy. |

Department of Chemical Sciences, University of Naples Federico II, via Cintia 21, I-80126 Naples, Italy. |

Department of Chemical Sciences, University of Naples Federico II, via Cintia 21, I-80126 Naples, Italy |

Publication type: Journal Article

Publication date: 2021-01-01

Elsevier

Journal: Pharmacology and Therapeutics

Quartile SCImago

Quartile WOS

Impact factor: 13.5

ISSN: 01637258, 1879016X

DOI: 10.1016/j.pharmthera.2020.107649

Copy DOI

Pharmacology

Pharmacology (medical)

Abstract

First studies on thrombin-inhibiting DNA aptamers were reported in 1992, and since then a large number of anticoagulant aptamers has been discovered. TBA – also named HD1, a 15-mer G-quadruplex (G4)-forming oligonucleotide – is the best characterized thrombin binding aptamer, able to specifically recognize the protein exosite I, thus inhibiting the conversion of soluble fibrinogen into insoluble fibrin strands. Unmodified nucleic acid-based aptamers, in general, and TBA in particular, exhibit limited pharmacokinetic properties and are rapidly degraded in vivo by nucleases. In order to improve the biological performance of aptamers, a widely investigated strategy is the introduction of chemical modifications in their backbone at the level of the nucleobases, sugar moieties or phosphodiester linkages. Besides TBA, also other thrombin binding aptamers, able to adopt a well-defined G4 structure, e.g. mixed duplex/quadruplex sequences, as well as homo- and hetero-bivalent constructs, have been identified and optimized. Considering the growing need of new efficient anticoagulant agents associated with the strong therapeutic potential of these thrombin inhibitors, the research on thrombin binding aptamers is still a very hot and intriguing field. Herein, we comprehensively described the state-of-the-art knowledge on the DNA-based aptamers targeting thrombin, especially focusing on the optimized analogues obtained by chemically modifying the oligonucleotide backbone, and their biological performances in therapeutic applications.

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Citations by publishers

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Elsevier	Elsevier, 9, 14.75% Elsevier 9 publications, 14.75%
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	5 10 15 20 25

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Riccardi C. et al. G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects // Pharmacology and Therapeutics. 2021. Vol. 217. p. 107649.

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Riccardi C., Napolitano E., Platella C., Musumeci D., Montesarchio D. G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects // Pharmacology and Therapeutics. 2021. Vol. 217. p. 107649.

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RIS Copy

TY - JOUR

DO - 10.1016/j.pharmthera.2020.107649

UR - https://doi.org/10.1016/j.pharmthera.2020.107649

TI - G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects

T2 - Pharmacology and Therapeutics

AU - Riccardi, C.

AU - Napolitano, Ettore

AU - Platella, Chiara

AU - Musumeci, Domenica

AU - Montesarchio, Daniela

PY - 2021

DA - 2021/01/01 00:00:00

PB - Elsevier

SP - 107649

VL - 217

SN - 0163-7258

SN - 1879-016X

ER -

BibTex

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BibTex Copy

@article{2021_Riccardi,

author = {C. Riccardi and Ettore Napolitano and Chiara Platella and Domenica Musumeci and Daniela Montesarchio},

title = {G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects},

journal = {Pharmacology and Therapeutics},

year = {2021},

volume = {217},

publisher = {Elsevier},

month = {jan},

url = {https://doi.org/10.1016/j.pharmthera.2020.107649},

pages = {107649},

doi = {10.1016/j.pharmthera.2020.107649}

}

Found error?

Publisher

Elsevier

Journal

Pharmacology and Therapeutics

Quartile SCImago

Quartile WOS

Impact factor

13.5

ISSN

01637258 (Print)
1879016X (Electronic)