Amino‐Acid‐Derived Naphthalenediimides as Versatile G‐Quadruplex Binders

Răsădean, Dora M.; Sheng, Bin; Dash, Jyotirmaee; Pantoş, G. Dan

doi:10.1002/chem.201700957

Cited by 26 publications

(27 citation statements)

References 66 publications

(127 reference statements)

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“…GQR was identified among several boron–dipyrromethene (BODIPY) derivatives as a particular parallel G4‐preferred light‐up probe (93del: 5′‐G 4 TG 3 AG 2 AG 3 T over c‐ myc and c‐ kit parallel G4s; Figure f) . NDI 3 was developed as a ligand with specificity for a c‐ kit G4, in which a planar core naphthalenediimide was functionalized with two lysines with tert ‐butyloxycarbonyl (Boc)‐protected side chains (Figure g) . The preference for this interaction possibly relies on the specific contact with the loops or grooves.…”

Section: Addressing the Specificity Of Ligands To Particular G4smentioning

confidence: 99%

Ligand Design to Acquire Specificity to Intended G‐Quadruplex Structures

Asamitsu

Bando

Sugiyama

2018

Chemistry A European J

139

116

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A G-quadruplex is a nucleic acid secondary structure that is adopted by guanine-rich sequences, and is considered to be relevant in various pharmacological and biological contexts. G-Quadruplexes have also attracted great attention in the field of DNA nanotechnology because of their extremely high thermal stability and the availability of many defined structures. To date, a large repertory of DNA/RNA G-quadruplex-interactive ligands has been developed by numerous laboratories. Several relevant reviews have also been published that have helped researchers to grasp the full scope of G-quadruplex research from its outset to the present. This review focuses on the G-quadruplex ligands that allow targeting of specific G-quadruplexes. Moreover, unique ligands, successful methodologies, and future perspectives in relation to specific G-quadruplex recognition are also addressed.

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Section: Addressing the Specificity Of Ligands To Particular G4smentioning

confidence: 99%

Ligand Design to Acquire Specificity to Intended G‐Quadruplex Structures

Asamitsu

Bando

Sugiyama

2018

Chemistry A European J

139

116

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“…NDIs functionalized with disubstituted aminoacids were synthetized and investigated as G4 binders [79]: one of them (compound 55 , Table 3) showed selective stabilization of the KIT2 sequence (ΔT m 14.6 °C, Table 4) coupled with a slight destabilization of the KIT 1 sequence in vitro.…”

Section: Ndis As G4-mediated Downregulators Of Gene Expressionmentioning

confidence: 99%

Naphthalene Diimides as Multimodal G-Quadruplex-Selective Ligands

et al. 2019

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G-quadruplexes are four-stranded nucleic acids structures that can form in guanine-rich sequences. Following the observation that G-quadruplexes are particularly abundant in genomic regions related to cancer, such as telomeres and oncogenes promoters, several G-quadruplex-binding molecules have been developed for therapeutic purposes. Among them, naphthalene diimide derivatives have reported versatility, consistent selectivity and high affinity toward the G-quadruplex structures. In this review, we present the chemical features, synthesis and peculiar optoelectronic properties (absorption, emission, redox) that make naphtalene diimides so versatile for biomedical applications. We present the latest developments on naphthalene diimides as G-quadruplex ligands, focusing on their ability to bind G-quadruplexes at telomeres and oncogene promoters with consequent anticancer activity. Their different binding modes (reversible versus irreversible/covalent) towards G-quadruplexes and their additional use as antimicrobial agents are also presented and discussed.

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“…One of the compounds demonstrated selective stabilization of the KIT2 sequence (ΔT max 14.6°C) in combination with a slight destabilization of the KIT1 sequence in vitro. 86 The crystal structures of three complexes with telomeric intramolecular human G4 showed that two of the four strongly basic N-methylpiperazine groups can be replaced by less basic morpholine groups without the loss of intermolecular interactions in the grooves of G4. The new compounds retain a high affinity for human telomeric quadruplex DNA, but are 10 times more effective against the pancreatic cancer cell line MIA PaCa-2 with IC 50 values of ~10 nM.…”

Section: Biological Activity Of Diazapyrenes 21 Antiproliferative Amentioning

confidence: 99%

“…One of the compounds demonstrated selective stabilization of the KIT2 sequence (Δ T max 14.6°C) in combination with a slight destabilization of the KIT1 sequence in vitro . 86 …”

Section: Biological Activity Of Diazapyrenesmentioning

confidence: 99%

Diazapyrenes: interaction with nucleic acids and biological activity

Zhirov

Kovalev

Ulshina

et al. 2020

Chem Heterocycl Comp

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DNA is the pharmacological target for many drugs or compounds currently undergoing clinical trials. 1 Developing new drugs and improving the effects of existing drugs is a complex task that goes beyond improving the specificity of a drug with respect to its biological target. Since in many cases only a small fraction of the administered drug compound reaches the pharmacological target, it is necessary to develop strategies for increasing the accumulation of the drug near cellular DNA. The drug delivery strategy should be aimed at increasing circulation time, enhancing tissue-specific accumulation, increasing the efficiency of cellular and nuclear uptake in addition to high specificity and affinity to DNA. The complexity of biological systems makes it difficult to simultaneously incorporate all of these factors into a single drug development algorithm. However, focusing on specificity is relatively simple because the structure of DNA is well known. 2 Currently, there are many strategies of exploiting the known DNA structure for specific binding of drug compounds. One approach is to use small molecules that can recognize nucleic acids and bind to specific areas of DNA, major or minor grooves, or integrate between DNA bases arranged in specific nucleotide sequences. One of the well-studied DNA targets of drugs is the G-quadruplexes (G4). 3 G4 are secondary nucleic acid structures that can form in single-stranded guanine-rich sequences under physiological conditions. 4 Four guanines are paired via hydrogen bonds to form G-quadruplexes. These structures are further stabilized in the presence of metal ions such as potassium ions. Studies of their stability showed that these noncanonical secondary DNA structures are capable of destabilizing the double helix, since many G4 structures are thermodynamically more stable than double-stranded DNA (dsDNA), and their denaturation rate is significantly lower. 5 G4 sequences in eukaryotes play key regulatory functions, including transcriptional regulation of promoters 5b and gene enhancers, 5b,6 translation, 5b,6,7 epigenetic regulation of chromatin 8 and DNA recombination. 5b,8

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Amino‐Acid‐Derived Naphthalenediimides as Versatile G‐Quadruplex Binders

Cited by 26 publications

References 66 publications

Ligand Design to Acquire Specificity to Intended G‐Quadruplex Structures

Ligand Design to Acquire Specificity to Intended G‐Quadruplex Structures

Naphthalene Diimides as Multimodal G-Quadruplex-Selective Ligands

Diazapyrenes: interaction with nucleic acids and biological activity

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