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.

Structural properties and anticoagulant/cytotoxic activities of heterochiral enantiomeric thrombin binding aptamer (TBA) derivatives / Virgilio, A.; Esposito, V.; Pecoraro, A.; Russo, A.; Vellecco, V.; Pepe, A.; Bucci, M.; Russo, G.; Galeone, A.. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 48:22(2020), pp. 12556-12565. [10.1093/nar/gkaa1109]

Structural properties and anticoagulant/cytotoxic activities of heterochiral enantiomeric thrombin binding aptamer (TBA) derivatives

Virgilio A.
Co-primo
;
Esposito V.
Co-primo
;
Pecoraro A.;Russo A.;Vellecco V.;Bucci M.;Russo G.
Penultimo
;
Galeone A.
Ultimo
2020

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.
2020
Structural properties and anticoagulant/cytotoxic activities of heterochiral enantiomeric thrombin binding aptamer (TBA) derivatives / Virgilio, A.; Esposito, V.; Pecoraro, A.; Russo, A.; Vellecco, V.; Pepe, A.; Bucci, M.; Russo, G.; Galeone, A.. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 48:22(2020), pp. 12556-12565. [10.1093/nar/gkaa1109]
File in questo prodotto:
File Dimensione Formato  
2020 NAR.pdf

accesso aperto

Descrizione: articolo principale
Tipologia: Versione Editoriale (PDF)
Licenza: Dominio pubblico
Dimensione 2.37 MB
Formato Adobe PDF
2.37 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/848068
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 12
social impact