Related Experiment Video
Updated: Aug 6, 2026

A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
Published on: April 16, 2021
Discovery of bioactive small-molecule inhibitor of poly adp-ribose polymerase: implications for energy-deficient
Stephen M Altmann1, Andrey Muryshev, Elisa Fossale
1Massachusetts General Institute for Neurodegenerative Disease and Harvard Medical School, Department of Neurology, Massachusetts General Hospital, Charlestown, 02129, USA.
Abstract:
Poly (ADP-ribose) polymerase (PARP1) is a nuclear protein that, when overactivated by oxidative stress-induced DNA damage, ADP ribosylates target proteins leading to dramatic cellular ATP depletion. We have discovered a biologically active small-molecule inhibitor of PARP1. The discovered compound inhibited PARP1 enzymatic activity in vitro and prevented ATP loss and cell death in a surrogate model of oxidative stress in vivo. We also investigated a new use for PARP1 inhibitors in energy-deficient cells by using Huntington's disease as a model. Our results showed that insult with the oxidant hydrogen peroxide depleted cellular ATP in mutant cells below the threshold of viability. The protective role of PARP1 inhibitors against oxidative stress has been shown in this model system.
Related Concept Videos
Biosynthesis of Nucleic Acids
Biosynthesis of Polysaccharides
Types of RNA
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Other Glycolytic Pathways
Riboswitches
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
Ribozymes
Ribozymes can be...
