Design of a selective chemical probe for class I PDZ domains.
Covalent labeling has been widely used for structural and functional analyses of proteins. To target a wide range of PDZ domains, we designed a chemical scaffold mimicking the E/D-T/S-XV peptide, which is a PDZ domain that binds ligands in higher occurrence. A chemical probe (2) that contained this moiety alkylated diverse PDZ domains, including NHERF-1 PDZ2, and differentially visualized the cellular proteome.
Fujii
Naoaki
N
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. naoaki.fujii@stjude.org
Shelat
Anang
A
Hall
Randy A
RA
Guy
R Kiplin
RK
D000478:Alkylation; D002352:Carrier Proteins / Q000187:drug effects*; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D007202:Indicators and Reagents; D008024:Ligands; D008565:Membrane Proteins; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D010750:Phosphoproteins / Q000737:chemistry; D011485:Protein Binding; D020543:Proteome / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry
D002352:Carrier Proteins; D007202:Indicators and Reagents; D008024:Ligands; D008565:Membrane Proteins; D015335:Molecular Probes; C484659:PDZK1 protein, human; D010455:Peptides; D010750:Phosphoproteins; D020543:Proteome; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor