Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Novel Mechanism for Activation of SIRT1

Published: Wednesday, April 24, 2013
Last Updated: Wednesday, April 24, 2013
Bookmark and Share
Assay format allows for simple, sensitive detection of sirtuin activity on any desired substrate.

Merck Millipore has introduced the SIRTainty™ Class III HDAC assay which allows for simple, sensitive detection of sirtuin activity on any desired substrate.

The assay utilizes a novel patent-pending technology for the sensitive detection of all known sirtuin family members.

Unlike conventional assays that are dependent upon a single pre-labeled fluorescently tagged substrate, the SIRTainty™ Class III HDAC assay employs untagged acetylated peptide substrates.

This approach not only enables unparalleled flexibility in the choice of sirtuin isoform and peptide substrate, but also eliminates the potential for artifacts due to the use of artificial substrates containing bulky fluorophores.

A recent report published in the March 8th issue of Science (Hubbard et al. 2013) from the lab of David Sinclair, Ph.D., Harvard Medical School, described a novel mechanism for the allosteric activation of SIRT1 by small molecules.

In order to perform this work, the authors employed the SIRTainty™ assay to measure SIRT1 deacetylation of native peptide substrates.

"The SIRTainty™ assay is a superior assay for measuring sirtuin activity," said David Sinclair, Ph.D., corresponding author and co-inventor of the SIRTainty™ assay. "Unlike other HDAC assays that limit flexibility in experimental design, there is no fluorophore on the substrate. Any native substrate can be tested."

Sirtuins are a class of enzyme that removes acetyl groups from a variety of proteins that play key roles in multiple biological processes.

These enzymes, also known as class III HDAC (histone deacetylases), have been implicated in a variety of age-related diseases such as cancer, Alzheimer's disease and Type 2 diabetes. Sirtuins have emerged as key targets for drug development.

"The ability to measure SIRT1 deacetylation using fluorophore-free peptides derived from physiological substrates was critical in enabling our mechanistic analysis of SIRT1 activation," noted Basil P. Hubbard, Ph.D., lead author of the article and co-inventor of the SIRTainty™ assay.

Hubbard continued, "The SIRTainty™ assay is amenable to the biochemical study of multiple mammalian sirtuin deacetylases and their homologs in lower organisms. Because of this, it has the potential to facilitate the discovery and characterization of small-molecule modulators of other sirtuins."

Resveratrol, a compound found in red wine, has been shown to activate SIRT1 in vivo. However, there is controversy in the field as to whether the effect of Resveratrol on SIRT1 is direct.

Previously it was shown that although Resveratrol was capable of activating SIRT1 deacetylation of a fluorescently-tagged substrate in vitro, it was unable to do so using the corresponding non-tagged peptide.

However, by using the technology now offered in the SIRTainty™ assay, the team of Harvard researchers showed that Resveratrol and synthetic SIRT1 activators can directly enhance SIRT1 deacetylation in vitro using natural amino acid substrates and SIRT1 targets containing specific hydrophobic motifs.

Their work suggests that the metabolic benefits of Resveratrol are due to direct activation of SIRT1 enzymatic activity.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Merck Millipore Announces New Genomic Biomarker Services
Genetic and epigenetic technologies added to established CRO services for biomarker development, validation and testing.
Wednesday, December 05, 2012
Merck Millipore Announces Opening of its GMP Bioproduction Facility in France
Enables accelerated process development and production of proteins/monoclonal antibodies.
Friday, September 21, 2012
Scientific News
FNIH Launches Project to Evaluate Biomarkers in Cancer Patients
Company has announced that it has launched a new project to evaluate the effectiveness of liquid biopsies as biomarkers in colorectal cancer patients.
HIV Particles Used to Trap Intact Mammalian Protein Complexes
Belgian scientists from VIB and UGent developed Virotrap, a viral particle sorting approach for purifying protein complexes under native conditions.
Potential “Good Fat” Biomarker
New method to measure the activity of energy consuming brown fat cells could ease the testing weight loss drugs.
Computational Model Finds New Protein-Protein Interactions
Researchers at University of Pittsburgh have discovered 500 new protein-protein interactions (PPIs) associated with genes linked to schizophrenia.
New Insights into Gene Regulation
Researchers have solved the three-dimensional structure of a gene repression complex that is known to play a role in cancer.
Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Soy Shows Promise as Natural Anti-Microbial Agent
Soy isoflavones and peptides may inhibit the growth of microbial pathogens that cause food-borne illnesses, according to a new study from University of Guelph researchers.
Potential Target for Revolutionary Antibiotics
An international team of including the Lomonosov Moscow State University researchers discovered which enzyme enables Escherichia coli bacterium (E. coli) to breathe.
DNA Barcodes Gone Wild
A team of researchers at University of Toronto’s Donnelly Centre and Sinai Health System’s Lunenfeld-Tanenbaum Research Institute (LTRI) has developed a new technology that can stitch together DNA barcodes inside a cell to simultaneously search amongst millions of protein pairs for protein interactions.
Biomarkers for Profiling Prostate Cancer Patients
Exiqon A/S has announced the publication of validation of prognostic microRNA biomarkers for the aggressiveness of prostate cancer in independent cohorts.
Scroll Up
Scroll Down
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!