Development of Second Generation Activity-Based Chemical Probes for Sirtuins
NAD<sup>+</sup> (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 exten...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/1/11 |
| _version_ | 1797543838721507328 |
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| author | Alyson M. Curry Elizabeth Barton Wenjia Kang Daniel V. Mongeluzi Yana Cen |
| author_facet | Alyson M. Curry Elizabeth Barton Wenjia Kang Daniel V. Mongeluzi Yana Cen |
| author_sort | Alyson M. Curry |
| collection | DOAJ |
| description | NAD<sup>+</sup> (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. |
| first_indexed | 2024-03-10T13:51:27Z |
| format | Article |
| id | doaj.art-4cdf12b35cff42a3b082e91acee2f121 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T13:51:27Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4cdf12b35cff42a3b082e91acee2f1212023-11-21T02:04:53ZengMDPI AGMolecules1420-30492020-12-012611110.3390/molecules26010011Development of Second Generation Activity-Based Chemical Probes for SirtuinsAlyson M. Curry0Elizabeth Barton1Wenjia Kang2Daniel V. Mongeluzi3Yana Cen4Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23219, USADepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23219, USADepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23219, USADepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23219, USADepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23219, USANAD<sup>+</sup> (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.https://www.mdpi.com/1420-3049/26/1/11sirtuinactivity-basedchemical probes |
| spellingShingle | Alyson M. Curry Elizabeth Barton Wenjia Kang Daniel V. Mongeluzi Yana Cen Development of Second Generation Activity-Based Chemical Probes for Sirtuins Molecules sirtuin activity-based chemical probes |
| title | Development of Second Generation Activity-Based Chemical Probes for Sirtuins |
| title_full | Development of Second Generation Activity-Based Chemical Probes for Sirtuins |
| title_fullStr | Development of Second Generation Activity-Based Chemical Probes for Sirtuins |
| title_full_unstemmed | Development of Second Generation Activity-Based Chemical Probes for Sirtuins |
| title_short | Development of Second Generation Activity-Based Chemical Probes for Sirtuins |
| title_sort | development of second generation activity based chemical probes for sirtuins |
| topic | sirtuin activity-based chemical probes |
| url | https://www.mdpi.com/1420-3049/26/1/11 |
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