Biologically active oligodeoxyribonucleotides. Part 12:1 N2-Methylation of 2′-deoxyguanosines enhances stability of parallel G-quadruplex and anti-HIV-1 activity

Koizumi, Makoto; Akahori, Keika; Ohmine, Toshinori; Tsutsumi, Sadami; Sone, Junko; Kaneko, Masakatsu; Kimura, Satoshi; Shimada, Kaoru

doi:10.1016/s0960-894x(00)00432-7

Cited by 25 publications

(27 citation statements)

References 13 publications

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“…Structural-activity relationship analysis showed that the presence of a DNA duplex and hydrophobic groups was crucial for the anti-HIV-1 activity observed, although the locations of the hydrophobic groups in the duplex and the sequence composition seemed not to be critical to the activity of the respective DNA duplexes tested. The modified DNA duplexes showed anti-HIV-1 activity at low M concentrations comparable to those of a previously described G-quadruplex HIV-1 entry inhibitor (17)(18)(19)(20)(21)(22)(23)(24). These duplex inhibitors were found to be interacting with the HIV-1 gp41 NHR deep pocket to prevent 6HB formation between the gp41 NHR and CHR.…”

Section: Discussionsupporting

confidence: 67%

“…In contrast to Hotoda's quadruplex inhibitors d(TGGGAG) 4 (17)(18)(19)(20)(21)(22)(23)(24), the duplex inhibitors reported in this paper can be extensively modified based on the location of the hydrophobic groups and skeleton length, thereby presenting more opportunities for modification.…”

Section: Discussionmentioning

confidence: 99%

“…These aptamers fold into defined three-dimensional (3D) structures and interact with HIV-1-associated proteins, such as HIV-1 reverse transcriptases (6,7), RNase H (8), Tat proteins (9), integrase (10)(11)(12)(13), and surface glycoproteins (14,15). A subcategory of aptamers possess an additional intermolecular assembly feature such as the quadruplex d(TGGGAG) 4 described by Hotoda et al, which was assembled by four 6-mer G-rich sequences in parallel with the 5=-end attaching to aromatic substituents of adequate size, such as tert-butyldiphenylsilyl (TBDPS) and 4=4-dimethoxytriphenyl (DMT) (16)(17)(18)(19)(20)(21)(22)(23)(24). These quadruplexes are aptamer-like since they interact with the V3 loop or the CD4 binding site on viral gp120, preventing viral adhesion and fusion with target cells (17,25,26).…”

mentioning

confidence: 99%

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DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

Xu¹,

Cai²,

Chen

et al. 2013

Antimicrob Agents Chemother

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Discovery of new drugs for the treatment of AIDS typically possessing unique structures associated with novel mechanisms of action has been of great importance due to the quick drug-resistant mutations of HIV-1 strains. The work presented in this report describes a novel class of DNA duplex-based HIV-1 fusion inhibitors. Hydrophobic groups were introduced into a DNA duplex skeleton either at one end, at both ends, or in the middle. These modified DNA duplexes inhibited fusion between HIV-1 and human cell membranes at micro-or submicromolar concentrations. Respective inhibitors adopted an aptamer pattern instead of a base-pairing interaction pattern. Structure-activity relationship studies of the respective DNA duplexes showed that the rigid and negatively charged DNA skeletons, in addition to the presence of hydrophobic groups, were crucial to the anti-HIV-1 activity of these compounds. A fluorescent resonance energy transfer (FRET)-based inhibitory assay showed that these duplex inhibitors interacted with the primary pocket in the gp41 N-terminal heptad repeat (NHR) instead of interacting with the lipid bilayers.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

Xu¹,

Cai²,

Chen

et al. 2013

Antimicrob Agents Chemother

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show abstract

“…Some have been addressed to modifications that enhance the activity against human immunodeficiency virus (HIV-1) [90][91][92][93][94], or the antiproliferative activity for a number of tumor cell lines [95]. Other studies report biophysical and structural analyses of modified quadruplexes of telomeric sequences [96][97][98][99][100].…”

Section: Modified Aptamersmentioning

confidence: 99%

Quadruplex-Forming Oligonucleotides as Tools in Anticancer Therapy and Aptamers Design: Energetic Aspects

Petraccone

Barone²,

Giancola³

2005

CMCACA

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Recent investigations on the G-quadruplex motif propose a new strategy for the making of antitumour drugs. Quadruplex-drug complexes have been suggested to inhibit telomerase activity; further, aptamers based on the quadruplex motif have been proved useful as tools aimed at binding and inhibiting particular proteins, thus serving as pharmaceutically active agents. However, the design of new aptamers is difficult because many factors affecting their activity and stability have not still been clarified. The knowledge of the energetics of quadruplex formation is a crucial point in view of their potential therapeutic utilization both as targets as well as therapeutic agents. In this review the energetic aspects of both quadruplex assembly and quadruplex-ligand interactions are discussed together with a summary of recent studies on physico-chemical properties in solution of quadruplex structures obtained from synthetic aptamers, including PNA-DNA chimeras.

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“…Tetramolecular complexes, which have recently displayed interesting biological properties [28][29][30], always show the four strands in a parallel orientation. Further, quadruplex DNA is an excellent module for the design of novel devices for nanotechnology applications, because of its extreme rigidity and self-recognition properties [31].…”

Section: Introductionmentioning

confidence: 99%

Physico-chemical analysis of G-quadruplex containing bunch-oligonucleotides

Petraccone¹,

Martino

Duro

et al. 2007

International Journal of Biological Macromolecules

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Biologically active oligodeoxyribonucleotides. Part 12:1 N2-Methylation of 2′-deoxyguanosines enhances stability of parallel G-quadruplex and anti-HIV-1 activity

Cited by 25 publications

References 13 publications

DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

DNA Duplexes with Hydrophobic Modifications Inhibit Fusion between HIV-1 and Cell Membranes

Quadruplex-Forming Oligonucleotides as Tools in Anticancer Therapy and Aptamers Design: Energetic Aspects

Physico-chemical analysis of G-quadruplex containing bunch-oligonucleotides

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