Herein, pyrenecarboxaldehyde@graphene oxide (Pyc@GO) sheets with highly efficient electrochemiluminescence (ECL) as emitters were prepared by a noncovalent combination to develop a neoteric ECL biosensing platform for the ultrasensitive assessment of human apurinic/apyrimidinic endonuclease1 (APE1) activity. Impressively, the pyrenecarboxaldehyde (Pyc) molecules were able to form stable polar functional groups on the surface of GO sheets through the noncovalent π-π stacking mechanism to prevent intermolecular restacking and simultaneously generate Pyc@GO sheets. Compared with the tightly packed PAH nanocrystals, the Pyc@GO sheets significantly reduced internal filtering effects and diminished nonactivated emitters to enhance ECL intensity and achieve strong ECL emission. Furthermore, the APE1-activated initiators could trigger the recyclable cascade amplified system based on the synergistic cross-activation between catalytic hairpin assembly (CHA) and DNAzyme, which improved the signal amplification and transduction ability. Consequently, the developed ECL platform for the detection of APE1 activity displayed exceptional sensitivity with a low detection limit of 4.6 × 10 U·mL ranging from 10 to 10 U·mL. Therefore, the proposed strategy holds great promise for the future development of sensitive and reliable biosensing platforms for the detection of various biomarkers.
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http://dx.doi.org/10.1021/acssensors.3c02425 | DOI Listing |
Antioxid Redox Signal
December 2024
Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, Parkville, Australia.
Inflammation and oxidative stress play crucial roles in the development and progression of skeletal muscle diseases. This review aims to examine the existing evidence regarding the involvement and inhibition of APE1/Ref-1 (apurinic/apyrimidinic endonuclease 1/redox factor 1) in diseases, then extrapolate this evidence to the context of skeletal muscle and discuss the potential beneficial effects of APE1/Ref-1 inhibition in ameliorating myopathy with a particular focus on dystrophic pathology. Currently, therapeutic interventions targeting pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (NRF2), have shown limited efficacy in both clinical and preclinical settings.
View Article and Find Full Text PDFJ Phys Chem B
December 2024
Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive West, Lethbridge, Alberta, Canada T1K 3M4.
Despite the remarkable resistance of the nucleic acid phosphodiester backbone to degradation affording genetic stability, the P-O bond must be broken during DNA repair and RNA metabolism, among many other critical cellular processes. Nucleases are powerful enzymes that can enhance the uncatalyzed rate of phosphodiester bond cleavage by up to ∼10-fold. Despite the most well accepted hydrolysis mechanism involving two metals (M to activate a water nucleophile and M to stabilize the leaving group), experimental evidence suggests that some nucleases can use a single metal to facilitate the chemical step, a controversial concept in the literature.
View Article and Find Full Text PDFChem Sci
December 2024
Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, Institute of Developmental Biology and Regenerative Medicine, College of Chemistry and Chemical Engineering, Southwest University Chongqing 400715 P. R. China
Utilizing the cGAS-STING pathway to combat immune evasion is one of the most promising strategies for enhancing cancer immunotherapy. However, current techniques for activating the cGAS-STING pathway often face a dilemma, mainly due to the balance between efficacy and safety. Here, we develop a uracil base lesion-gated dumbbell DNA nanodevice (UBLE) that allows on-demand activation and termination of the cGAS-STING pathway in tumor cells, thereby enhancing cancer immunotherapy.
View Article and Find Full Text PDFChem Res Toxicol
December 2024
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, Missouri 65211, United States.
Apurinic/apyrimidinic endonuclease 1 (APE1) is a central enzyme in the base excision repair (BER) pathway. APE1 catalyzes incision of the phosphodiester linkage on the 5'-side of apurinic/apyrimidinic (AP) sites during the repair of damaged nucleobases in cellular DNA. Inhibition of this enzyme can potentiate the action of DNA-damaging chemotherapeutic agents.
View Article and Find Full Text PDFBMB Rep
December 2024
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
Base excision repair (BER) is an essential cellular mechanism that repairs small, non-helix-distorting base lesions in DNA, resulting from oxidative damage, alkylation, deamination, or hydrolysis. This review highlights recent advances in understanding the molecular mechanisms of BER enzymes through single-molecule studies. We discuss the roles of DNA glycosylases in lesion recognition and excision, with a focus on facilitated diffusion mechanisms such as sliding and hopping that enable efficient genome scanning.
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