A general screening strategy for peptide-based fluorogenic ligands: Probes for dynamic studies of PDZ domain-mediated interactions

Matthieu Sainlos, Wendy S. Iskenderian, Barbara Imperiali
J. Am. Chem. Soc.. 2009-05-20; 131(19): 6680-6682
DOI: 10.1021/ja900371q

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1. J Am Chem Soc. 2009 May 20;131(19):6680-2. doi: 10.1021/ja900371q.

A general screening strategy for peptide-based fluorogenic ligands: probes for
dynamic studies of PDZ domain-mediated interactions.

Sainlos M(1), Iskenderian WS, Imperiali B.

Author information:
(1)Department of Chemistry, Massachusetts Institute of Technology, 77
Massachusetts Avenue, Cambridge, Massachusetts 02139-4307, USA.

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.

DOI: 10.1021/ja900371q
PMCID: PMC2828873
PMID: 19388649 [Indexed for MEDLINE]

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