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#34114295   2021/06/11 To Up

Liquid droplet formation and facile cytosolic translocation of IgG in the presence of attenuated cationic amphiphilic lytic peptides.

Fc region binding peptide conjugated with attenuated cationic amphiphilic lytic peptide L17E trimer [FcB(L17E)3] was designed for immunoglobulin G (IgG) delivery into cells. Particle-like liquid droplets were generated by mixing Alexa Fluor 488 labeled IgG (Alexa488-IgG) with FcB(L17E)3. Droplet contact with the cellular membrane led to spontaneous influx and distribution of Alexa488-IgG throughout cells in serum containing medium. Involvement of cellular machinery accompanied by actin polymerization and membrane ruffling was suggested for the translocation. Alexa488-IgG negative charges were crucial in liquid droplet formation with positively charged FcB(L17E)3. Binding of IgG to FcB(L17E)3 may not be necessary. Successful intracellular delivery of Alexa Fluor 594-labeled anti-nuclear pore complex antibody and anti-mCherry-nanobody tagged with supernegatively charged green fluorescence protein allowed binding to cellular targets in the presence of FcB(L17E)3.
Takahiro Iwata, Hisaaki Hirose, Kentarou Sakamoto, Yusuke Hirai, Jan Vincent V Arafiles, Misao Akishiba, Miki Imanishi, Shiroh Futaki

1364 related Products with: Liquid droplet formation and facile cytosolic translocation of IgG in the presence of attenuated cationic amphiphilic lytic peptides.

1mg20 20 100 96 tests100 0.1ml20 20 100 µg

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#34105487   // To Up

[The Role of Zyxin in Regulating Platelet Cytoskeleton Distribution].

To investigate the regulatory effect of zyxin on the distribution of platelet cytoskeleton.
Bin Cheng, Rong Yan, Su-Qin Zhang, Meng-Nan Yang, Ke-Sheng Dai

2278 related Products with: [The Role of Zyxin in Regulating Platelet Cytoskeleton Distribution].

100 UG2 Pieces/Box12 Pieces/Box

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#34094839   2020/09/19 To Up

Mechanism of allosteric activation of SIRT6 revealed by the action of rationally designed activators.

The recent discovery of activator compounds binding to an allosteric site on the NAD-dependent protein lysine deacetylase, sirtuin 6 (SIRT6) has attracted interest and presents a pharmaceutical target for aging-related and cancer diseases. However, the mechanism underlying allosteric activation of SIRT6 by the activator MDL-801 remains largely elusive because no major conformational changes are observed upon activator binding. By combining molecular dynamics simulations with biochemical and kinetic analyses of wild-type SIRT6 and its variant M136A, we show that conformational rotation of 2-methyl-4-fluoro-5-bromo substituent on the right phenyl ring (R-ring) of MDL-801, which uncovers previously unseen hydrophobic interactions, contributes to increased activating deacetylation activity of SIRT6. This hypothesis is further supported by the two newly synthesized MDL-801 derivatives through the removal of the 5-Br atom on the R-ring (MDL-801-D1) or the restraint of the rotation of the R-ring (MDL-801-D2). We further propose that the 5-Br atom serves as an allosteric driver that controls the ligand allosteric efficacy. Our study highlights the effect of allosteric enzyme catalytic activity by activator binding and provides a rational approach for enhancing deacetylation activity.
Shaoyong Lu, Yingyi Chen, Jiacheng Wei, Mingzhu Zhao, Duan Ni, Xinheng He, Jian Zhang

2832 related Products with: Mechanism of allosteric activation of SIRT6 revealed by the action of rationally designed activators.

5 G5mg5mg5mg5mg100 IU5mg5mg250ul0.1 mg 100 G

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#34090266   // To Up

EPIDEMIOLOGICAL INDICATORS OF DENTAL MORBIDITY OF CHILDREN AS AN INDICATOR OF ADVERSE ENVIRONMENTAL INFLUENCE.

The aim: Is to study the ecological and hygienic situation in the living area of 6-year-old children in terms of drinking water (micro- and macroelements), to identify its relationship with the state of mineral metabolism in children's mouths, prevalence and intensity of temporary and permanent caries.
Petro A Hasiuk, Nataliia O Gevkaliuk, Maryana Ya Pynda, Anna B Vorobets, Tetiana I Dzetsiukh, Volodymyr Yе Pudiak, Yurii V Smiianov

1937 related Products with: EPIDEMIOLOGICAL INDICATORS OF DENTAL MORBIDITY OF CHILDREN AS AN INDICATOR OF ADVERSE ENVIRONMENTAL INFLUENCE.

5 G100 μg100 assays1 ml100 ul100 μg100ug Lyophilized100ug Lyophilized

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#34080035   2021/06/03 To Up

A 15-min non-competitive homogeneous assay for microcystin and nodularin based on time-resolved Förster resonance energy transfer (TR-FRET).

Simple and rapid methods are required for screening and analysis of water samples to detect cyanobacterial cyclic peptide hepatotoxins: microcystin/nodularin. Previously, we reported a highly sensitive non-competitive heterogeneous assay for microcystin/nodularin utilizing a generic anti-immunocomplex (anti-IC) single-chain fragment of antibody variable domains (scFv) isolated from a synthetic antibody library together with a generic adda ((2S,3S,4E,6E,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid)-specific monoclonal antibody (Mab) recognizing the common adda part of the microcystin/nodularin. Using the same antibody pair, here we report a homogeneous non-competitive assay for microcystin/nodularin based on TR-FRET (time-resolved Förster resonance energy transfer) measurement. The anti-IC scFv labeled with Alexa Fluor 680 and the Mab labeled with europium enabled the FRET process to occur in the presence of microcystin/nodularin. The TR-FRET signal is proportional to the toxin concentration in the sample. The rapid (15 min) homogeneous assay without requiring any washing step detected all the tested nine toxin variants (microcystin-LR, -dmLR, -RR, -dmRR, -YR, -LY, -LF -LW, and nodularin-R). Very good signal to blank ratio (~13) was achieved using microcystin-LR and the sample detection limit (blank+3SD of blank) for microcystin-LR was ~0.3 μg/L (~0.08 μg/L in 80-μL reaction well). The practical application of the TR-FRET assay was demonstrated with water samples spiked with microcystin-LR as well as with environmental water. The average recoveries of microcystin-LR from spiked water ranged from 65 to 123%. Good correlation (r = 0.73 to 0.99) with other methods (liquid chromatography-mass spectrometry and previously reported heterogeneous assay) was found when environmental samples were analyzed. The developed wash-free assay has the potential to play as a quick screening tool to detect microcystin/nodularin from water below the World Health Organization's guideline limit (1 μg/L of microcystin-LR).
Sultana Akter, Urpo Lamminmäki

1278 related Products with: A 15-min non-competitive homogeneous assay for microcystin and nodularin based on time-resolved Förster resonance energy transfer (TR-FRET).

100 tests100 assays10 plates100 assays1 plate96 Tests1,000 tests50 assays

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#34063555   2021/05/15 To Up

Malignancy Rate of Indeterminate Findings on FDG-PET/CT in Cutaneous Melanoma Patients.

The use of -2-Fluor-2-desoxy-D-glucose Positron Emission Tomography/Computed Tomography FDG-PET/CT in clinical routine for staging, treatment response monitoring and post treatment surveillance in metastatic melanoma patients has noticeably increased due to significant improvement of the overall survival rate in melanoma patients. However, determining the dignity of the findings with increased metabolic activity on FDG-PET/CT can be sometimes challenging and may need further investigation.
Ken Kudura, Florentia Dimitriou, Daniela Mihic-Probst, Urs J Muehlematter, Tim Kutzker, Lucas Basler, Robert Förster, Reinhard Dummer, Joanna Mangana, Lars Husmann, Irene A Burger, Michael Christoph Kreissl

2742 related Products with: Malignancy Rate of Indeterminate Findings on FDG-PET/CT in Cutaneous Melanoma Patients.

1 Set1 Set1 Set1 Set1 Set1 Set1 Set1 Set

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#34059711   2021/05/31 To Up

Fluorescent base analogues in gapmers enable stealth labeling of antisense oligonucleotide therapeutics.

To expand the antisense oligonucleotide (ASO) fluorescence labeling toolbox beyond covalent conjugation of external dyes (e.g. ATTO-, Alexa Fluor-, or cyanine dyes), we herein explore fluorescent base analogues (FBAs) as a novel approach to endow fluorescent properties to ASOs. Both cytosine and adenine analogues (tC, tC, 2CNqA, and pA) were incorporated into a 16mer ASO sequence with a 3-10-3 cEt-DNA-cEt (cEt = constrained ethyl) gapmer design. In addition to a comprehensive photophysical characterization, we assess the label-induced effects on the gapmers' RNA affinities, RNA-hybridized secondary structures, and knockdown efficiencies. Importantly, we find practically no perturbing effects for gapmers with single FBA incorporations in the biologically critical gap region and, except for pA, the FBAs do not affect the knockdown efficiencies. Incorporating two cytosine FBAs in the gap is equally well tolerated, while two adenine analogues give rise to slightly reduced knockdown efficiencies and what could be perturbed secondary structures. We furthermore show that the FBAs can be used to visualize gapmers inside live cells using fluorescence microscopy and flow cytometry, enabling comparative assessment of their uptake. This altogether shows that FBAs are functional ASO probes that provide a minimally perturbing in-sequence labeling option for this highly relevant drug modality.
Jesper R Nilsson, Tom Baladi, Audrey Gallud, Dženita Baždarević, Malin Lemurell, Elin K Esbjörner, L Marcus Wilhelmsson, Anders Dahlén

1618 related Products with: Fluorescent base analogues in gapmers enable stealth labeling of antisense oligonucleotide therapeutics.

10reactions 10reactions 10reactions10reactions 10reactions 10reactions (20 µl each)10reactions

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