WARF: P06108US

Methods for Determining Protein Binding Specificity Using Peptide Libraries


John Denu, Adam Garske

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a novel, high throughput method for determining deacetylase substrate specificity.
OVERVIEWSilent information regulator (SIRT) genes encode sirtuins, a highly conserved class of protein deacetylases that have been implicated in physiological processes and diseases states ranging from aging to cancer.
THE INVENTIONUW-Madison researchers have developed a novel, high throughput method for determining deacetylase substrate specificity. The method uses a one-bead, one-compound (OBOC) acetyl-peptide library with a quantum dot tagging strategy and automated bead sorting. The library is screened using a deacetylase, such as a SIRT protein, to identify the most efficiently deacetylated sequences. Each bead is then labeled with a streptavidin-coated quantum dot. After fluorescent bead sorting, the brightest and most deacetylated beads can be sequenced via mass spectrometry.
  • Optimized SIRT substrates could serve as the basis for designing peptidomimetic SIRT inhibitors, ultimately leading to treatments for cancer, aging, diabetes, HIV, cardiovascular disorders and/or neurodegenerative diseases.
  • Allows context-specific identification of preferred peptide substrates, rather than globally preferred amino acids, at each location
  • Sequence information from the library could be used to generate acetyl-peptide specific antibodies for Western blot analysis, immunoprecipitation studies or antibody-based inhibitors.
  • Library may be used to created super substrates for the in vivo generation of the novel metabolite O-acetyl-ADP-ribose.
STAGE OF DEVELOPMENTWhen the researchers screened a 5-mer OBOC peptide library of over 100,000 unique sequences, they found that SIRT1 shows considerable preference for particular substrate sequences.
For More Information About the Inventors
Related Intellectual Property
  • Garske A.L., Oliver S.S., Wagner E.K., Musselman C.A., LeRoy G., Garcia B.A., Kutateladze T.G. and Denu J.M. 2010. Combinatorial Profiling of Chromatin Binding Modules Reveals Multisite Discrimination. Nat. Chem. Bio. 6, 283-290.
Contact Information
For current licensing status, please contact Rafael Diaz at or 608-960-9847.
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