Modulation of protein–ligand interactions by photocleavage of a cyclic peptide using phosphatidylinositol 3‐kinase SH3 domain as model system |
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| Authors: | Isao Takahashi Shigeki Kuroiwa Hanna E Lindfors Lionel A Ndamba Yoshitaka Hiruma Tatsuo Yajima Nobuyuki Okishio Marcellus Ubbink Shun Hirota |
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| Institution: | 1. Graduate School of Materials Science, Nara Institute of Science and Technology, 8916‐5 Takayama, Ikoma, Nara 630‐0192, Japan;2. Department of Physical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi‐cho, Misasagi, Yamashina‐ku, Kyoto 607‐8414, Japan;3. Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands;4. Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa 920‐8640, Japan |
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| 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 (Kd: 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. |
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| Keywords: | protein– peptide interaction phosphatidylinositol 3‐kinase SH3 domain RLP1 peptide photocleavage cyclic peptide photomodulation |
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