Kinetic characterization of small DNA-binding molecules interacting with a DNA strand on a quartz crystal microbalance

Furusawa, Hiroyuki; Nakayama, H.; Funasaki, Mariko; Okahata, Yoshio

doi:10.1016/j.ab.2015.09.015

Cited by 19 publications

(21 citation statements)

References 28 publications

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“…Acla binds slightly stronger to DNA than Epi. In the literature, the affinity of Acla to different DNA molecules has been reported to be in the low nM to low µM range [36][37][38] , whilst compounds similar to Epi, like Doxo, that differs from Epi in the stereochemistry of the 4'-OH group, binds to DNA in the nM range 39 . It is known that most of the anthracyclines have a preference for GC-rich sequences.…”

Section: Epirubicin and Aclarubicin Disturb Rela-dna Bindingmentioning

confidence: 99%

DNA damage independent inhibition of NF-κB transcription by anthracyclines

Chora

Pedroso

Pejanovic

et al. 2020

Preprint

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Transcriptional programs leading to induction of a large number of genes can be rapidly initiated by the activation of only few selected transcription factors. Upon stimulation of macrophages with microbial-associated molecular patterns (MAMPs), the activation of the nuclear factor kappa B (NF-kB) family of transcription factors triggers inflammatory responses that, left uncontrolled, can lead to excessive inflammation with life-threatening consequences for the host. Here we identify and characterize a novel effect of Anthracyclines, a class of drugs currently used as potent anticancer drugs, in the regulation of NF-kB transcriptional activity in BMDMs, in addition to the previously reported DNA damage and histone eviction. Anthracyclines, including Doxorubicin, Daunorubicin and Epirubicin, disturb the complexes formed between the NF-kB subunit RelA and its DNA binding sites, to limit NF-kB-dependent gene transcription during inflammatory responses, including of pivotal pro-inflammatory mediators such as TNF.We observed that suppression of inflammation can also be mediated by Aclarubicin, Doxorubicinone and the newly developed Dimethyl-doxorubicin, which share anticancer properties with the other Anthracyclines, but do not induce DNA damage in the tested concentrations. This novel mechanism of action of Anthracyclines, contributing to the reduction of inflammation, is thus independent of the activation of DNA damage responses and may be relevant for the development of novel strategies targeting immunemediated inflammatory diseases. The nuclear factor kappa B (NF-kB) family of transcription factors, comprising RelA, RelB, c-Rel, p100 and p105, plays a prominent role in regulating inflammation 2 . All members share the N-terminal REL-homology domain (RHD) responsible for IkB binding, nuclear localization, dimerization and DNA binding. On their C-terminal region, RelA, RelB and c-Rel contain a transactivation domain (TAD), responsible for their transcriptional activity 3 . While NF-kB activation is strictly required to trigger the inflammatory response, uncontrolled NF-kB activity can result in a failure to resolve inflammation, contributing to the establishment of a growing number of pathological conditions 4 . At steady state, transcriptionally active NF-kB family members, of which RelA is the most abundant, are retained in the cytoplasm by their interaction with inhibitors of kB (IkB) molecules. IkBa phosphorylation in response to a variety of stimuli leads to its proteosomal degradation, a step required for RelA nuclear localization, DNA binding and initiation of gene transcription 5 3 . RelA-dependent IkBa re-synthesis is essential for its nuclear eviction and the timely termination of NF-kB transcriptional activity 6 7 . Posttranslational modifications within both RHD and TAD add an additional layer of control over RelA-dependent gene transcription, activating or repressing its transcriptional activity by controlling RelA association with IkB, nuclear localization, interaction with transcriptional cofactors, D...

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Section: Epirubicin and Aclarubicin Disturb Rela-dna Bindingmentioning

confidence: 99%

DNA damage independent inhibition of NF-κB transcription by anthracyclines

Chora

Pedroso

Pejanovic

et al. 2020

Preprint

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“…The sensor cell, with a volume of 500 μL, was equipped with an AT-cut quartz plate with a diameter of 8.7 mm, which had a gold electrode of 5.7 mm 2 in area attached at the bottom of the cell [27][28][29]. CD films were prepared on the gold electrode ( Figure 2).…”

Section: Preparation Of α- β- and γ-Cd Films On Qcm Sensor Surfacesmentioning

confidence: 99%

“…The mass change (∆m) can be calculated from the frequency change (∆F) using Equation (1). Specific details are described in previous papers [27][28][29].…”

Section: Qcm Setup and Odorant Molecule Detectionmentioning

confidence: 99%

“…In this study, we demonstrated the capture capability of CDs for ethyl butyrate and limonene, which were selected as model odorant molecules for fruit fragrances, using a highly sensitive 27-MHz QCM device [27][28][29] (Figure 1). CD thin films prepared with α-, β-, or γ-CD were expected to possess molecular-size selectivity, resulting in pattern recognition.…”

Section: Introductionmentioning

confidence: 99%

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Detection of Odorant Molecules in the Gaseous Phase Using α-, β-, and γ-Cyclodextrin Films on a Quartz Crystal Microbalance

et al. 2018

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Abstract:There is an interest in sensors for the detection of odorant molecules in the gaseous phase, especially those related to the fragrance of fruits, because odorant sensing is useful for on-site quality control of agricultural products. Previously, gas-chromatographic methods requiring bench-top devices were used for odorant-molecule detection. Herein, we report an odorant sensor based on cyclodextrins (CDs) as a stable odorant receptor, using a highly mass-sensitive and quantitative 27-MHz quartz crystal microbalance (QCM) device, which has the advantage of possible incorporation into portable devices. When ethyl butyrate (a model odorant molecule for fruit fragrances) was flowed onto a QCM plate modified with α-, β-, or γ-CD network films, a decrease in frequency was observed (corresponding to an increase in mass), owing to the capture of odorant molecules by CD molecules. The CD films were capable of capturing and releasing odorant molecules, depending on the type of CD (α-, β-, or γ-CD). Thus, these sensors are reusable for odorant-molecule sensing, and are applicable to pattern recognition of odorant molecules. Thus, sensors based on CD films combined with a QCM handheld device could be applied to monitoring the condition of fruits.

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“…Hexagonal packing of DNA and RNA was observed for DNA and RNA complexes with Cetyltrimethyl Ammonium Bromide (CTBA) and for Dimethyldioctadecyl Ammonium Bromide (DDAB) complexes is observed lamellar structure. Variations in the internal spacing and degree of long-range ordering are dependent on both surfactant type and concentrations of added salt [19][20][21][22][23][24][25][26][27][28][29]. When we increased the amount of salt into our complexes, we observed that the d spacing (d=2Π/r) are increased.…”

mentioning

confidence: 99%

A Thermodynamic Study on Hydration and Dehydration of DNA and RNA −Amphiphile Complexes

Heidari¹

2016

J Bioengineer & Biomedical Sci

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Kinetic characterization of small DNA-binding molecules interacting with a DNA strand on a quartz crystal microbalance

Cited by 19 publications

References 28 publications

DNA damage independent inhibition of NF-κB transcription by anthracyclines

DNA damage independent inhibition of NF-κB transcription by anthracyclines

Detection of Odorant Molecules in the Gaseous Phase Using α-, β-, and γ-Cyclodextrin Films on a Quartz Crystal Microbalance

A Thermodynamic Study on Hydration and Dehydration of DNA and RNA −Amphiphile Complexes

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