Biologically active oligodeoxyribonucleotides. Part 11: The least phosphate-modification of quadruplex-forming hexadeoxyribonucleotide TGGGAG, bearing 3′- and 5′-end-modification, with anti-HIV-1 activity

Koizumi, Makoto; Koga, Ryota; Hotoda, Hitoshi; Ohmine, Toshinori; Furukawa, Hidehiko; Agatsuma, Toshinori; Nishigaki, Toshinori; Abe, Kōji; Tsutsumi, Sadami; Sone, Junko; Kaneko, Masakatsu; Kimura, Satoshi; Shimada, Kaoru

doi:10.1016/s0968-0896(98)80021-7

Cited by 19 publications

(11 citation statements)

References 23 publications

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“…Later on, Koizumi et al synthesized a set of G-rich oligonucleotides and identified the hexadeosyribonucleotide d(TGGGAG), known as Hotoda’s sequence, [49,50]. Several authors have used the Hotoda’s sequence as a lead sequence to make a series of modifications at the 5′ and 3′ ends of the molecule or mutations in the sequence that allowed to find molecules with high anti-HIV activity [50,51,52,53,54,55,56]. …”

Section: Aptamers For Virus Diagnosis and Treatmentmentioning

confidence: 99%

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

González

Martı́n

Fernández³

et al. 2016

Pharmaceuticals

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Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment.

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Section: Aptamers For Virus Diagnosis and Treatmentmentioning

confidence: 99%

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

González

Martı́n

Fernández³

et al. 2016

Pharmaceuticals

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“…The aptamer was shown to have synergistic anti-HIV effects together with AZT against HIV in human cell lines [94]. Various hexanucleotides, based around the d(TGGGAG) Hotoda sequence also exhibited strong anti-HIV properties [23,95,96]. A particularly exciting extension of these ideas are to use anti-gp120 aptamers (although in this case 2'F-substituted RNA aptamers) to deliver siRNA into HIV infected cells [97].…”

Section: G-quadruplex Dna Aptamers Against Infective Agentsmentioning

confidence: 99%

G-quadruplex DNA Aptamers and their Ligands: Structure, Function and Application

Tucker¹,

Shum²,

Tanner

2012

CPD

162

126

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Highly specific and tight-binding nucleic acid aptamers have been selected against a variety of molecular targets for over 20 years. A significant proportion of these oligonucleotides display G-quadruplex structures, particularly for DNA aptamers, that enable molecular recognition of their ligands. G-quadruplex structures couple a common scaffold to varying loop motifs that act in target recognition. Here, we review DNA G-quadruplex aptamers and their ligands from a structural and functional perspective. We compare the diversity of DNA G-quadruplex aptamers selected against multiple ligand targets, and consider structure with a particular focus on dissecting the thrombin binding aptamer - thrombin interaction. Therapeutic and analytical applications of DNA G-quadruplex aptamers are also discussed. Understanding DNA G-quadruplex aptamers carries implications not only for therapeutics and diagnostics, but also in the natural biochemistry of guanine-rich nucleic acids.

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“…Several folded quadruplexes can target nucleolin, a nucleolar protein involved in multiple aspects of cell growth, thereby inhibiting cell proliferation in some human tumour cell lines ( 8 ). A tetrameric quadruplex is able to target HIV integrase, ( 9 ) the enzyme responsible for the insertion of viral DNA into the host genome, and the HIV envelope-mediated cell fusion is inhibited by the parallel tetrameric quadruplex formed by T 2 G 4 T 2 ( 10 ). This quadruplex drug is modified with phosphorothioate nucleotide linkages, which shows that the use of nucleic acid analogues may be useful in drug therapy with quadruplex molecules.…”

Section: Introductionmentioning

confidence: 99%

NMR solution structures of LNA (locked nucleic acid) modified quadruplexes

Nielsen

Arar²,

Petersen³

2006

Nucleic Acids Research

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We have determined the NMR solution structures of the quadruplexes formed by d(TGLGLT) and d(TL4T), where L denotes LNA (locked nucleic acid) modified G-residues. Both structures are tetrameric, parallel and right-handed and the native global fold of the corresponding DNA quadruplex is retained upon introduction of the LNA nucleotides. However, local structural alterations are observed owing to the locked LNA sugars. In particular, a distinct change in the sugar–phosphate backbone is observed at the G2pL3 and L2pL3 base steps and sequence dependent changes in the twist between tetrads are also seen. Both the LNA modified quadruplexes have raised thermostability as compared to the DNA quadruplex. The quadruplex-forming capability of d(TGLGLT) is of particular interest as it expands the design flexibility for stable parallel LNA quadruplexes and shows that LNA nucleotides can be mixed with DNA or other modified nucleic acids. As such, LNA-based quadruplexes can be decorated by a variety of chemical modifications. Such LNA quadruplex scaffolds might find applications in the developing field of nanobiotechnology.

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Biologically active oligodeoxyribonucleotides. Part 11: The least phosphate-modification of quadruplex-forming hexadeoxyribonucleotide TGGGAG, bearing 3′- and 5′-end-modification, with anti-HIV-1 activity

Cited by 19 publications

References 23 publications

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

G-quadruplex DNA Aptamers and their Ligands: Structure, Function and Application

NMR solution structures of LNA (locked nucleic acid) modified quadruplexes

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