Journal
JOURNAL OF BIOMOLECULAR SCREENING
Volume 20, Issue 7, Pages 842-848Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1087057115588512
Keywords
self-assembled monolayers; deacetylase; label-free; peptide array
Funding
- Phase II SBIR [NSF10-607]
Ask authors/readers for more resources
Lysine acetylation plays a critical role in cellular regulation and is implicated in human disease. Sirtuin deacetylases remove acetyl groups from modified lysine residues, and sirtuin 3 (SIRT3) has been identified as a target for cancer therapeutics. Robust and high-throughput screening methods for these targets will be important to the development of therapeutics. This article describes the use of self-assembled monolayer desorption/ionization mass spectrometry, or SAMDI-MSa label-free drug discovery toolto characterize SIRT3 activity and discover inhibitors. SAMDI-MS was used to analyze a peptide array having 361 distinct acetylated peptides to identify an active SIRT3 substrate (GYK(Ac)RGC). This peptide was used in a screen of 100,000 small molecules to identify inhibitors of SIRT3. A total of 306 SIRT3 inhibitors were identified, with one compound, SDX-437, having an IC50 of 700 nM with >100-fold selectivity for SIRT3 over SIRT1.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available