Tetra-end-linked oligonucleotides forming DNA G-quadruplexes: a new class of aptamers showing anti-HIV activity

Oliviero, Giorgia; Amato, Jussara; Borbone, Nicola; D’Errico, Stefano; Galeone, Aldo; Mayol, Luciano; Haider, Shozeb; Olubiyi, Olujide O.; Hoorelbeke, Bart; Balzarini, Jan; Piccialli, Gennaro

doi:10.1039/c0cc02866e

Cited by 38 publications

(36 citation statements)

References 20 publications

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“…As an example, tetra-end linked oligonucleotides having a cluster of four TG 4 T sequences, arranged in a parallel G4 were investigated for anti-HIV activity and showed potencies in the submicromolar range. The authors speculate that Arg190, the only conserved residue in the hypervariable V3 loop of GP120 represents a key site for aptamer binding, recognition being generally driven by electrostatic forces [22].…”

Section: Introductionmentioning

confidence: 99%

The evolving world of protein-G-quadruplex recognition: A medicinal chemist’s perspective

2011

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The physiological and pharmacological role of nucleic acids structures folded into the non canonical G-quadruplex conformation have recently emerged. Their activities are targeted at vital cellular processes including telomere maintenance, regulation of transcription and processing of the pre-messenger or telomeric RNA. In addition, severe conditions like cancer, fragile X syndrome, Bloom syndrome, Werner syndrome and Fanconi anemia J are related to genomic defects that involve G-quadruplex forming sequences. In this connection G-quadruplex recognition and processing by nucleic acid directed proteins and enzymes represents a key event to activate or deactivate physiological or pathological pathways. In this review we examine protein-G-quadruplex recognition in physiologically significant conditions and discuss how to possibly exploit the interactions' selectivity for targeted therapeutic intervention.

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Section: Introductionmentioning

confidence: 99%

The evolving world of protein-G-quadruplex recognition: A medicinal chemist’s perspective

2011

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“…Furthermore, in HTM , the incorporation of an 8‐methyl‐2′‐deoxyguanosine (M) at the 5′‐end of the G‐run stabilized the quadruplex structure. Importantly, it should be noted that, according to some authors,31 the interaction with the target protein would involve the quadruplex groove regions near the G4 and A5 residues, which (being quite distant from the 5′‐end, where the M residue was introduced) are not particularly affected by this modification, as showed by NMR and molecular modeling.…”

Section: Discussionmentioning

confidence: 93%

Structural Investigations on the Anti‐HIV G‐Quadruplex‐Forming Oligonucleotide TGGGAG and Its Analogues: Evidence for the Presence of an A‐Tetrad

et al. 2012

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Several anti-HIV aptamers adopt DNA quadruplex structures. Among these, "Hotoda's aptamer" (base sequence TGGGAG) was one of the first to be discovered. Although it has been the topic of some recent research, no detailed structural investigations have been reported. Here we report structural investigations on this aptamer and analogues with related sequences, by using UV, CD, and NMR spectroscopy as well as electrophoretic techniques. The addition of a 3'-end thymine has allowed us to obtain a single, investigable quadruplex structure. Data clearly point to the presence of an A-tetrad. Furthermore, the effects of the incorporation of an 8-methyl-2'-deoxyguanosine at the 5'-end of the G-run were investigated.

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“…This drawback could be circumvented by designing parallel G-quadruplexes containing IPSs with the suitable sequences, which, thanks to their monomolecular nature, would be characterized by higher formation rate and stabilities, besides preserving the main features of the original parallel G-quadruplex structures. A similar approach has been successful applied in the monomolecular tetra-end-linked (TEL-ODNs) version of the Hotoda's aptamer ( 64 , 65 ).…”

Section: Discussionmentioning

confidence: 99%

Monomolecular G-quadruplex structures with inversion of polarity sites: new topologies and potentiality

Virgilio

Russo

Amato

et al. 2017

Nucleic Acids Research

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In this paper, we report investigations, based on circular dichroism, nuclear magnetic resonance spectroscopy and electrophoresis methods, on three oligonucleotide sequences, each containing one 3′-3′ and two 5′-5′ inversion of polarity sites, and four G-runs with a variable number of residues, namely two, three and four (mTG2T, mTG3T and mTG4T with sequence 3′-TGnT-5′-5′-TGnT-3′-3′-TGnT-5′-5′-TGnT-3′ in which n = 2, 3 and 4, respectively), in comparison with their canonical counterparts (TGnT)4 (n = 2, 3 and 4). Oligonucleotides mTG3T and mTG4T have been proven to form very stable unprecedented monomolecular parallel G-quadruplex structures, characterized by three side loops containing the inversion of polarity sites. Both G-quadruplexes have shown an all-syn G-tetrad, while the other guanosines adopt anti glycosidic conformations. All oligonucleotides investigated have shown a noteworthy antiproliferative activity against lung cancer cell line Calu 6 and colorectal cancer cell line HCT-116 p53−/−. Interestingly, mTG3T and mTG4T have proven to be mostly resistant to nucleases in a fetal bovine serum assay. The whole of the data suggest the involvement of specific pathways and targets for the biological activity.

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Tetra-end-linked oligonucleotides forming DNA G-quadruplexes: a new class of aptamers showing anti-HIV activity

Abstract: The biophysical and biological properties of unprecedented anti-HIV aptamers are presented. The most active aptamer (1L) shows a significant affinity to the HIV protein gp120.

Cited by 38 publications

References 20 publications

The evolving world of protein-G-quadruplex recognition: A medicinal chemist’s perspective

The evolving world of protein-G-quadruplex recognition: A medicinal chemist’s perspective

Structural Investigations on the Anti‐HIV G‐Quadruplex‐Forming Oligonucleotide TGGGAG and Its Analogues: Evidence for the Presence of an A‐Tetrad

Monomolecular G-quadruplex structures with inversion of polarity sites: new topologies and potentiality

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