Sensitive and selective detection of uracil-DNA glycosylase activity with a new pyridinium luminescent switch-on molecular probe

Lu, Yu‐Jing; Hu, Dong-Ping; Deng, Qiang; Wang, Zheng-Ya; Huang, Baohua; Fang, Yanxiong; Zhang, Kun; Wong, Wing‐Leung

doi:10.1039/c5an01158b

Cited by 30 publications

(24 citation statements)

References 36 publications

(52 reference statements)

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“…Additional studies with the symmetric scaffold reveal that 116 b is able to stabilize the human telomeric G4 with minimal effects on dsDNA. Also, the fluorescence intensity of 116 b is enhanced upon binding to G4 DNA substrates (specially c ‐ KIT1 and c ‐ MYC G4 ), whereas very weak fluorescence is observed upon treatment with nonforming G4 DNA substrates …”

Section: Modular G‐quadruplex Ligands As Selective Probesmentioning

confidence: 99%

Design of Modular G‐quadruplex Ligands

et al. 2018

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Guanine-rich nucleic acid sequences able to form four-stranded structures (G-quadruplexes, G4) play key cellular regulatory roles and are considered as promising drug targets for anticancer therapy. On the basis of the organization of their structural elements, G4 ligands can be divided into three major families: one, fused heteroaromatic polycyclic systems; two, macrocycles; three, modular aromatic compounds. The design of modular G4 ligands emerged as the answer to achieve not only more drug-like compounds but also more selective ligands by targeting the diversity of the G4 loops and grooves. The rationale behind the design of a very comprehensive set of ligands, with particular focus on the structural features required for binding to G4, is discussed and combined with the corresponding biochemical/biological data to highlight key structure-G4 interaction relationships. Analysis of the data suggests that the shape of the ligand is the major factor behind the G4 stabilizing effect of the ligands. The information here critically reviewed will certainly contribute to the development of new and better G4 ligands with application either as therapeutics or probes.

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Section: Modular G‐quadruplex Ligands As Selective Probesmentioning

confidence: 99%

Design of Modular G‐quadruplex Ligands

et al. 2018

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“…14,15 Cytosine-rich DNA strands can sensitively recognize acidic pH and fold into a quadruplex structure (i-motif structure) through CH + •C interactions. 16,17 The pH identification range of the i-motif forming strand (IFS) can be regulated by these sequences. Therefore, it is convenient to choose an IFS strand that can undergo cross-linking by forming an interchain quadruplex structure under weakly acidic pH, a typical physiological environment at the tumor site.…”

Section: Introductionmentioning

confidence: 99%

Robust and Tumor-Environment-Activated DNA Cross-Linker Driving Nanoparticle Accumulation for Enhanced Therapeutics

Zhang

Fan

et al. 2020

CCS Chem

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Agglomeration of therapeutic nanoparticles in response to tumor microenvironments is a promising approach to enhance drug accumulation and improve therapeutic efficacy. Cytosine-rich DNA sequences show potential as ideal cross-linkers to drive nanoparticle agglomeration because they can sensitively respond to weak acidity and form interchain folding. However, the in vivo application of DNA is generally limited by its poor biostability; as a consequence, modifications with unprotected DNA cross-linkers can enhance the accumulation of nanoparticles twofold at the tumor site. Facing this challenge, we have designed and developed a protection and tumor-environment activation strategy to enable the in vivo application of a DNA cross-linker. Specifically, reactive oxygen species (ROS)-responsive polyethylene glycol (PEG) was modified on the nanoparticle surface together with the DNA crosslinker, which protects DNA from degradation during the blood circulation; meanwhile, when arriving at the tumor site, the nanoparticles shed the PEG shell as a response to ROS to uncover and activate the DNA cross-linkers. Using this strategy, a sevenfold enhancement in tumor accumulation was achieved owing to both superior pH sensitivity and improved stability of DNA cross-linkers. Finally, significantly improved therapeutic efficacy in in vivo anticancer treatment was realized by using this agglomeration strategy driven by protected and stimuli-activated DNA cross-linkers.

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“…The excellent reproducibility and precision of the assay was also confirmed by a coefficient of variation (CV) less than 3% and a recovery ratio between 99 and 102% (Table ). These observations prove that the UDG activity assay procedure has the potential to reliably determine the amount of UDG present in human serum samples …”

Section: Resultsmentioning

confidence: 57%

Abasic Site‐Assisted Inhibition of Nicking Endonuclease Activity for the Sensitive Determination of Uracil DNA Glycosylase

Ahn

Lee

Park

et al. 2017

Biotechnology Journal

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We herein describe A novel strategy to accurately determine uracil DNA glycosylase (UDG) activity is described based on the finding that nicking endonuclease-assisted cleavage reaction can be regulated by the presence of abasic site. This strategy utilizes DNA probes rationally designed to contain uracil base at the cleavage site for nicking endonuclease, which is coupled to the isothermal nicking endonuclease amplification reaction (NEAR) method. In the absence of UDG, intact DNA probes generate a large number of double-stranded (ds) DNA products through the NEAR, but the presence of UDG that converts uracil base into abasic site suppresses nicking endonuclease activity and the subsequent NEAR. As a result, dsDNA products are not produced, which is simply monitored by the dsDNA specific fluorescence dye, SYBR green I. By employing this strategy, we sensitively determined the UDG activity down to 0.003 U mL with high specificity over other base excision enzymes. In addition, the diagnostic capability of this method was successfully verified by reliably assaying UDG present in a human serum sample.

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Sensitive and selective detection of uracil-DNA glycosylase activity with a new pyridinium luminescent switch-on molecular probe

Cited by 30 publications

References 36 publications

Design of Modular G‐quadruplex Ligands

Design of Modular G‐quadruplex Ligands

Robust and Tumor-Environment-Activated DNA Cross-Linker Driving Nanoparticle Accumulation for Enhanced Therapeutics

Abasic Site‐Assisted Inhibition of Nicking Endonuclease Activity for the Sensitive Determination of Uracil DNA Glycosylase

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