A general screening strategy for peptide-based fluorogenic ligands

• Main Authors: Sainlos, Matthieu (Contributor), Iskenderian, Wendy S. (Contributor), Imperiali, Barbara (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society, 2012-03-26T14:54:31Z.
• Subjects: Article
• Online Access: Get fulltext

A systematic and general approach for identifying efficient probes for class I PDZ domains based on environment-sensitive chromophores is presented. A series of peptides derived from the C-terminal sequence of Stargazin was first used with PDZ domains of PSD-95 and Shank3 to identify the optimal position and linker length for the 4-DMAP chromophore. The results were applied to well-characterized ligand sequences for each set of domains to generate high affinity probes that retain their native sequence specificity and yield remarkable fluorescence increases upon binding. These probes constitute efficient tools to study the dynamics and regulatory mechanisms of PDZ domain-mediated interactions.
Human Frontier Science Program (Strasbourg, France) ((RGP0007/2006)
National Institutes of Health (U.S.) (NIH Cell Migration Consortium (GM064346))
Marie Curie (Postdoctoral Fellowship (PICK-CPP))