Structural Properties and Anticoagulant/cytotoxic Activities of Heterochiral Enantiomeric Thrombin Binding Aptamer (TBA) Derivatives

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2020 Dec 3

PMID 33270863

Citations 8

Authors

Antonella Virgilio

Veronica Esposito

Annalisa Pecoraro

Annapina Russo

Valentina Vellecco

Antonietta Pepe

Mariarosaria Bucci

Giulia Russo

Aldo Galeone

Affiliations

Soon will be listed here.

Abstract

The thrombin binding aptamer (TBA) possesses promising antiproliferative properties. However, its development as an anticancer agent is drastically impaired by its concomitant anticoagulant activity. Therefore, suitable chemical modifications in the TBA sequence would be required in order to preserve its antiproliferative over anticoagulant activity. In this paper, we report structural investigations, based on circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMR), and biological evaluation of four pairs of enantiomeric heterochiral TBA analogues. The four TBA derivatives of the d-series are composed by d-residues except for one l-thymidine in the small TT loops, while their four enantiomers are composed by l-residues except for one d-thymidine in the same TT loop region. Apart from the left-handedness for the l-series TBA derivatives, CD and NMR measurements have shown that all TBA analogues are able to adopt the antiparallel, monomolecular, 'chair-like' G-quadruplex structure characteristic of the natural D-TBA. However, although all eight TBA derivatives are endowed with remarkable cytotoxic activities against colon and lung cancer cell lines, only TBA derivatives of the l-series show no anticoagulant activity and are considerably resistant in biological environments.

Citing Articles

Probing the Effects of Chemical Modifications on Anticoagulant and Antiproliferative Activity of Thrombin Binding Aptamer.

Virgilio A, Benigno D, Aliberti C, Bello I, Panza E, Smimmo M Int J Mol Sci. 2025; 26(1.

PMID: 39795992 PMC: 11719963. DOI: 10.3390/ijms26010134.

Synthesis of 2'--Methyl/2'--MOE-L-Nucleoside Derivatives and Their Applications: Preparation of G-Quadruplexes, Their Characterization, and Stability Studies.

Martin-Nieves V, Menendez-Mendez L, Fabrega C, Fernandez S, Sanghvi Y, Ferrero M ACS Omega. 2023; 8(47):44893-44904.

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Steric hindrance and structural flexibility shape the functional properties of a guanine-rich oligonucleotide.

Troisi R, Napolitano V, Rossitto E, Osman W, Nagano M, Wakui K Nucleic Acids Res. 2023; 51(16):8880-8890.

PMID: 37503836 PMC: 10484730. DOI: 10.1093/nar/gkad634.

Structural and Biological Features of G-Quadruplex Aptamers as Promising Inhibitors of the STAT3 Signaling Pathway.

Esposito V, Benigno D, Bello I, Panza E, Bucci M, Virgilio A Int J Mol Sci. 2023; 24(11).

PMID: 37298475 PMC: 10253491. DOI: 10.3390/ijms24119524.

Combining β-Carotene with 5-FU via Polymeric Nanoparticles as a Novel Therapeutic Strategy to Overcome uL3-Mediated Chemoresistance in p53-Deleted Colorectal Cancer Cells.

Carotenuto P, Pecoraro A, Brignola C, Barbato A, Franco B, Longobardi G Mol Pharm. 2023; 20(5):2326-2340.

PMID: 36976623 PMC: 10155186. DOI: 10.1021/acs.molpharmaceut.2c00876.

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