In the last years, G-rich oligonucleotides (GROs) able to form G-quadruplexes, have attracted considerable interest in biological and therapeutic fields. G-quadruplexes are among the most studied DNA structures because of the large variety of their biological properties ranging from anticancer to antiviral activities.(1) Recently, new findings on the anti-HIV-1 activity of ODNs forming G-quadruplex have been reported.(2) In this frame, here it is reported the synthesis of a mini-library of 5' and 3'-modified oligonucleotides with the Riboflavin (Vitamin B). The choice to insert the Riboflavin into lead sequence, has been inspired by the similarity with the hydrogen bond pattern of guanine, in addition to its excellent fluorescence properties that may be an useful tools for in vitro and in vivo studies. In order to allow the Riboflavin moiety similar to a nucleoside unit, the ribityl chain is rigidified by 2',4'-O-benzylidene group. The synthetic strategy is focused on the synthesis of two key intermidiates, the Riboflavin-Nucleoside phosphoramidite (I), useful for the synthesis of the 5'-end modified sequences and the CPG (Control Pore Glass) support anchoring the 5'-O-DMT-2',4'-O-benzyldene-riboflavin unit (II), fruitful for the synthesis of 3'-modified sequences. Using the phosphoramidite coupling automated protocol, the building block I was incorporated into oligonucleotides with a good yield. The new modified ODNs were assembled by standard automated DNA synthesis and after RP-HPLC purifications, they were analyzed by MALDI-TOF. Preliminary biophysical studies (CD, DSC and fluorescence studies) were carried out in order to evaluate the ability of modified ODNs to fold into G-quadruplex structures. Finally, their anti-HIV activity were evaluated.

Synthesis of ODN aptamers forming G-quadruplexes containing a nucleoside mimic based on Riboflavin / Romanucci, Valeria; Claes, Sandra; Schols, Dominique; Oliva, Rosario; Petraccone, Luigi; Zarrelli, Armando; DI FABIO, Giovanni. - (2018). (Intervento presentato al convegno Convegno Nazionale della Divisione di Chimica dei Sistemi Biologici tenutosi a Caserta nel 26-28 Settembre).

Synthesis of ODN aptamers forming G-quadruplexes containing a nucleoside mimic based on Riboflavin

Valeria Romanucci
;
Rosario Oliva;Luigi Petraccone;Armando Zarrelli;Giovanni Di Fabio
2018

Abstract

In the last years, G-rich oligonucleotides (GROs) able to form G-quadruplexes, have attracted considerable interest in biological and therapeutic fields. G-quadruplexes are among the most studied DNA structures because of the large variety of their biological properties ranging from anticancer to antiviral activities.(1) Recently, new findings on the anti-HIV-1 activity of ODNs forming G-quadruplex have been reported.(2) In this frame, here it is reported the synthesis of a mini-library of 5' and 3'-modified oligonucleotides with the Riboflavin (Vitamin B). The choice to insert the Riboflavin into lead sequence, has been inspired by the similarity with the hydrogen bond pattern of guanine, in addition to its excellent fluorescence properties that may be an useful tools for in vitro and in vivo studies. In order to allow the Riboflavin moiety similar to a nucleoside unit, the ribityl chain is rigidified by 2',4'-O-benzylidene group. The synthetic strategy is focused on the synthesis of two key intermidiates, the Riboflavin-Nucleoside phosphoramidite (I), useful for the synthesis of the 5'-end modified sequences and the CPG (Control Pore Glass) support anchoring the 5'-O-DMT-2',4'-O-benzyldene-riboflavin unit (II), fruitful for the synthesis of 3'-modified sequences. Using the phosphoramidite coupling automated protocol, the building block I was incorporated into oligonucleotides with a good yield. The new modified ODNs were assembled by standard automated DNA synthesis and after RP-HPLC purifications, they were analyzed by MALDI-TOF. Preliminary biophysical studies (CD, DSC and fluorescence studies) were carried out in order to evaluate the ability of modified ODNs to fold into G-quadruplex structures. Finally, their anti-HIV activity were evaluated.
2018
Synthesis of ODN aptamers forming G-quadruplexes containing a nucleoside mimic based on Riboflavin / Romanucci, Valeria; Claes, Sandra; Schols, Dominique; Oliva, Rosario; Petraccone, Luigi; Zarrelli, Armando; DI FABIO, Giovanni. - (2018). (Intervento presentato al convegno Convegno Nazionale della Divisione di Chimica dei Sistemi Biologici tenutosi a Caserta nel 26-28 Settembre).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/772237
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