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Development of Second Generation Activity-Based Chemical Probes for Sirtuins. | LitMetric

AI Article Synopsis

  • NAD-dependent protein deacylases, especially sirtuins, are crucial for adjusting cell functions in response to calorie restriction, promoting longevity and health.
  • Researchers created new chemical probes that effectively study sirtuin activity in complex biological samples, offering advantages over older methods.
  • These probes enable improved imaging of sirtuin activity changes and may aid in drug discovery targeting different sirtuin isoforms.

Article Abstract

NAD (nicotinamide adenine dinucleotide)-dependent protein deacylases, namely, the sirtuins, are important cell adaptor proteins that alter cell physiology in response to low calorie conditions. They are thought to mediate the beneficial effects of calorie restriction to extend longevity and improve health profiles. Novel chemical probes are highly desired for a better understanding of sirtuin's roles in various biological processes. We developed a group of remarkably simple activity-based chemical probes for the investigation of active sirtuin content in complex native proteomes. These probes harbor a thioacyllysine warhead, a diazirine photoaffinity tag, as well as a terminal alkyne bioorthogonal functional group. Compared to their benzophenone-containing counterparts, these new probes demonstrated improved labeling efficiency and sensitivity, shortened irradiation time, and reduced background signal. They were applied to the labeling of individual recombinant proteins, protein mixtures, and whole cell lysate. These cell permeable small molecule probes also enabled the cellular imaging of sirtuin activity change. Taken together, our study provides new chemical biology tools and future drug discovery strategies for perturbing the activity of different sirtuin isoforms.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792806PMC
http://dx.doi.org/10.3390/molecules26010011DOI Listing

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