Modulation of protein-ligand interactions by photocleavage of a cyclic peptide using phosphatidylinositol 3-kinase SH3 domain as model system.
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.
Takahashi
Isao
I
Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Kuroiwa
Shigeki
S
Lindfors
Hanna E
HE
Ndamba
Lionel A
LA
Hiruma
Yoshitaka
Y
Yajima
Tatsuo
T
Okishio
Nobuyuki
N
Ubbink
Marcellus
M
Hirota
Shun
S
D002942:Circular Dichroism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology / Q000528:radiation effects; D011487:Protein Conformation / Q000528:radiation effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014466:Ultraviolet Rays; D018909:src Homology Domains / Q000502:physiology*
D008024:Ligands; D010456:Peptides, Cyclic; D019869:Phosphatidylinositol 3-Kinases