The enzyme poly(ADP-ribose) glycohydrolase (PARG) performs a critical role in the repair of DNA single strand breaks (SSBs). However, a detailed understanding of its mechanism of action has been hampered by a lack of credible, cell-active chemical probes. Herein, we demonstrate inhibition of PARG with a small molecule, leading to poly(ADP-ribose) (PAR) chain persistence in intact cells. Moreover, we describe two advanced, and chemically distinct, cell-active tool compounds with convincing on-target pharmacology and selectivity. Using one of these tool compounds, we demonstrate pharmacology consistent with PARG inhibition. Further, while the roles of PARG and poly(ADP-ribose) polymerase (PARP) are closely intertwined, we demonstrate that the pharmacology of a PARG inhibitor differs from that observed with the more thoroughly studied PARP inhibitor olaparib. We believe that these tools will facilitate a wider understanding of this important component of DNA repair and may enable the development of novel therapeutic agents exploiting the critical dependence of tumors on the DNA damage response (DDR).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acschembio.6b00609 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Green Synthesis of Red Fluorescent Carbon Quantum Dots: Antioxidant, Hemolytic, Biocompatibility, and Photocatalytic Applications.
J Fluoresc
January 2025
Department of Stem Cell and Regenerative Medicine and Medical Biotechnology, Centre for Interdisciplinary Research, D. Y. Patil Education Society, Kolhapur, Maharashtra, India.
A straightforward one-step hydrothermal method is introduced for synthesizing highly efficient red fluorescence carbon dots (R-CQDs), utilizing Heena leaf (Lawsonia inermis) powder as the carbon precursor. The resulting R-CQDs exhibit excitation at 540 nm and emission at 675 nm, a high absolute photoluminescence (PL) with quantum yield of 40% in ethanol. Various physicochemical characterization was employed to confirm successful formation of R-CQDs including UV-Vis Spectroscopy, Fourier Transform Infrared (FT-IR) Spectroscopy, X-ray diffraction Spectroscopy, Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy.
View Article and Find Full Text PDFA catalytic perspective to nanomaterials reactivity-based toxicity; implications for single- and multiple-component nanomaterials (nanocomposites).
NanoImpact
January 2025
CSIC - Insituto de Catálisis y Petroleoquímica, Madrid, Spain.
The extended use of a given product normally precedes concerns about it. The reactivity-based nanotoxicity is a major concern that must be tackled from its fundamental understanding to its regulatory management. Moreover, concepts and ideas must seamlessly flow between relevant performers.
View Article and Find Full Text PDFHypochlorous Acid-Activatable NIR Fluorescence/Photoacoustic Dual-Modal Probe with High Signal-to-Background Ratios for Imaging of Liver Injury and Plasma Diagnosis of Sepsis.
ACS Sens
January 2025
Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Henan International Joint Laboratory of Smart Molecules and Identification and Diagnostic Functions, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China.
Hypochlorous acid can be employed as a biomarker for blood infection (such as sepsis) and tissue damage (such as drug-induced liver injury, DILI), and the diagnosis of tissue damage or blood infection can be achieved through the detection of hypochlorous acid in relevant biological samples. Considering the complex environment and the diverse interferences in living organisms and blood plasma, developing new detection methods for HClO with high signal-to-background ratios is particularly important, and it can improve the accuracy of detection and quality of imaging based on a higher contrast, which makes the detection of HClO clearer and more accurate. Here, based on the advantages of the NIR fluorescence/photoacoustic dual-modal probe, we reported a hypochlorous acid-activatable NIR fluorescence/photoacoustic dual-modal probe (NIRF-PA-HClO) based on the spirolactam ring-opening strategy in this paper.
View Article and Find Full Text PDFA SERS/colorimetric biosensor based on AuNSs@Ag core-shell Prussian blue nanozyme for non-interference and rapid detection of Staphylococcus aureus in milk.
Mikrochim Acta
January 2025
College of Chemistry and Chemical Engineering, Xinjiang Normal University, Urumqi, 830054, China.
A AuNSs@PB@Ag-Apt surface-enhanced Raman scattering (SERS) probe has been developed by embedding Prussian blue (PB) between Au core and Ag shell. The PB SERS probe illustrates strong SERS activity in the Raman silent region of 2070 cm, and has a zero background signal, ensuring high sensitivity for the detection of Staphylococcus aureus (S. aureus).
View Article and Find Full Text PDFFabrication of nanoparticles with precisely controllable plasmonic properties as tools for biomedical applications.
Nanoscale
January 2025
AIT Austrian Institute of Technology, Molecular Diagnostics, 1210 Vienna, Austria.
Metal nanoparticles are established tools for biomedical applications due to their unique optical properties, primarily attributed to localized surface plasmon resonances. They show distinct optical characteristics, such as high extinction cross-sections and resonances at specific wavelengths, which are tunable across the wavelength spectrum by modifying the nanoparticle geometry. These attributes make metal nanoparticles highly valuable for sensing and imaging in biology and medicine.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!