Modulation of protein–ligand interactions by photocleavage of a cyclic peptide using phosphatidylinositol 3-kinase SH3 domain as model system

✍ Scribed by Isao Takahashi; Shigeki Kuroiwa; Hanna E. Lindfors; Lionel A. Ndamba; Yoshitaka Hiruma; Tatsuo Yajima; Nobuyuki Okishio; Marcellus Ubbink; Shun Hirota

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 236 KB
• Volume: 15
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.1132

✦ Synopsis

Abstract

To photomodulate the interaction of the phosphatidylinositol 3‐kinase SH3 domain with a peptide ligand, a cyclic peptide (cyclic‐1) with a photolabile side chain‐to‐side chain linker was synthesized. The conformation of cyclic‐1 differs from that of the parent linear peptide, but becomes identical by UV‐irradiation. Accordingly, the binding affinity of cyclic‐1 to the SH3 domain increased upon conversion of the cyclic to a linear flexible structure by irradiation (K~d~: 3.4 ± 1.7 and 0.9 ± 0.3 mM, respectively). These results confirm the usefulness of a photocleavable peptide for photocontrol of peptide–protein interactions. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.