An overview of recent advances in duplex DNA recognition by small molecules

Bhaduri, Sayantan; Ranjan, Nihar; Arya, Dev P.

doi:10.3762/bjoc.14.93

Cited by 102 publications

(86 citation statements)

References 213 publications

(225 reference statements)

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“…Furthermore, 1 binds to ds‐DNA/RNA as a groove binder but, in contrast with most groove binders, it also interacts strongly with ss‐RNA, by acting as a spindle around which ss‐RNAs are wrapped due to a combination of electrostatic, H‐bonding and hydrophobic interactions. As most small molecule interactions with ss‐RNA are based on an intercalative binding mode, often combined with additional H‐bonding, whereby helicity of ss‐RNA is preserved or even enhanced, the binding mode of 1 presented herein is unique.…”

Section: Resultsmentioning

confidence: 99%

A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins

Ban

Griesbeck

Tomić

et al. 2020

Chemistry A European J

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A water‐soluble tetracationic quadrupolar bis‐triarylborane chromophore showed strong binding to ds‐DNA, ds‐RNA, ss‐RNA, as well as to the naturally most abundant protein, BSA. The novel dye can distinguish between DNA/RNA and BSA by fluorescence emission separated by Δtrueν˜ =3600 cm−1, allowing for the simultaneous quantification of DNA/RNA and protein (BSA) in a mixture. The applicability of such fluorimetric differentiation in vitro was demonstrated, strongly supporting a protein‐like target as a dominant binding site of 1 in cells. Moreover, our dye also bound strongly to ss‐RNA, with the unusual rod‐like structure of the dye, decorated by four positive charges at its termini and having a hydrophobic core, acting as a spindle for wrapping A, C and U ss‐RNAs, but not poly G, the latter preserving its secondary structure. To the best of our knowledge, such unmatched, multifaceted binding activity of a small molecule toward DNA, RNA, and proteins and the selectivity of its fluorimetric and chirooptic response makes the quadrupolar bis‐triarylborane a novel chromophore/fluorophore moiety for biochemical applications.

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Section: Resultsmentioning

confidence: 99%

A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins

Ban

Griesbeck

Tomić

et al. 2020

Chemistry A European J

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“…Narrowing of the minor groove is coupled to the local bending of DNA that allows formation of an extended protein-protein interface between NFAT and AP-1 (35), so the inhibitory effect of Compound 10 on complex formation could be explained if Compound 10 acts as a wedge that prevents narrowing of the minor groove and increases local rigidity of the DNA. If our goal were only to target ARRE-2, we could follow established principles to design compounds with higher specificity and higher affinity for the minor groove in this region of ARRE-2 (46)(47)(48). However, our purpose is to destabilize the broad class of complexes at NFAT:AP-1 composite sites relative to NFAT:partner complexes at other sites, and thus the appropriate target is the protein-protein interface.…”

Section: Discussionmentioning

confidence: 99%

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor

Mognol

González-Avalos

Ghosh

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The transcription factor nuclear factor of activated T cells (NFAT) has a key role in both T cell activation and tolerance and has emerged as an important target of immune modulation. NFAT directs the effector arm of the immune response in the presence of activator protein-1 (AP-1), and T cell anergy/exhaustion in the absence of AP-1. Envisioning a strategy for selective modulation of the immune response, we designed a FRET-based high-throughput screen to identify compounds that disrupt the NFAT:AP-1:DNA complex. We screened ∼202,000 small organic compounds and identified 337 candidate inhibitors. We focus here on one compound, N-(3-acetamidophenyl)-2-[5-(1H-benzimidazol-2-yl)pyridin-2-yl]sulfanylacetamide (Compound 10), which disrupts the NFAT:AP-1 interaction at the composite antigen-receptor response element-2 site without affecting the binding of NFAT or AP-1 alone to DNA. Compound 10 binds to DNA in a sequence-selective manner and inhibits the transcription of the Il2 gene and several other cyclosporin A-sensitive cytokine genes important for the effector immune response. This study provides proof-of-concept that small molecules can inhibit the assembly of specific DNA–protein complexes, and opens a potential new approach to treat human diseases where known transcription factors are deregulated.

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“…A developed 5-ethynyl-2′-deoxyuridine (EdU) can be detected by a fluorescent azide through a Cu(I)-catalyzed cycloaddition reaction. This fast and sensitive method has additional advantages over BrdU assay [17], which are lack of sample fixation and preservation of DNA structure [18]. Raman micro spectroscopy detects variations in Raman bands associated with O-H stretching in water [19].…”

Section: Cell Culture-based Assays To Evaluate Toxicity Associated Wimentioning

confidence: 99%

In Vitro Toxicity Testing of Nanomaterials

Martin¹,

Sarkar²

2019

Cell Culture

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Cell culture-based techniques are employed worldwide to assess risks to optimize design and handling of materials. Nano-scale particles particularly pose a challenge to the predictability of toxicity. This is due to the interplay of several factors including size, shape, surface properties, micro-environment, charge, electronic species etc., that affect the degree of cellular stress. Numerous assays could be employed to understand the nature of toxicity. Some of these include cytotoxicity, metabolic kinetics, modulation in cellular morphology. Various models such as primary cell culture and cell lines can also be employed that best suits a study. Signaling cascades could also be monitored in better understanding cellular responses holistically. Fluorescence microscopy can further be attempted in studying spatial and temporal variations of bio-markers. Ultimately any plethora of dose-response data, need to be streamlined for developing toxicity evaluation protocols that are accurate, cost effective and time saving.

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An overview of recent advances in duplex DNA recognition by small molecules

Cited by 102 publications

References 213 publications

A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins

A Quadrupolar Bis‐Triarylborane Chromophore as a Fluorimetric and Chirooptic Probe for Simultaneous and Selective Sensing of DNA, RNA and Proteins

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor

In Vitro Toxicity Testing of Nanomaterials

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