Kansai Photon Science Institute 　　| 　　The 60th KPSI Seminar, iQLS seminar Macrocyclic Peptide Drug Discovery Targeting Hepatocyte Growth Factor and the Receptor

Kansai Photon Science Institute >> KPSI Seminar >> Macrocyclic Peptide Drug Discovery Targeting Hepatocyte Growth Factor and the Receptor

Seminar

The 60th KPSI Seminar, iQLS seminar

Macrocyclic Peptide Drug Discovery Targeting Hepatocyte Growth Factor and the Receptor

Macrocyclic Peptide Drug Discovery Targeting Hepatocyte Growth Factor and the Receptor

Prof. MATSUMOTO Kunio
（Cancer Research Institute and WPI-Nano Life Science Institute, Kanazawa University）

abstract

Activation of hepatocyte growth factor (HGF)-MET receptor pathway drives cell proliferation, migration, morphogenesis (3-D tubulogenesis), and survival, thereby participates in regeneration of damaged tissues. On the other hand, aberrant activation of MET is associated with progression of cancer, particularly drug resistance and invasion-metastasis. By RaPID (Random Peptide Integrated Discovery) system, we obtained macrocyclic peptides that specifically bind to either HGF or MET receptor with 1-10 nM Kd values. The cross-linking of MET-binding macrocyclic peptides, that is the bivalent display of MET-binding peptide, conferred them an ability to activate MET. On the other hand, HGF-inhibitory peptide-8 (HiP-8) was obtained as an inhibitory macrocyclic peptide against HGF. Observation by high-speed atomic force microscopy indicated that the binding of HiP-8 to HGF suppress dynamic molecular movement of HGF. Using HiP-8 as a molecular probe, accumulation of HGF in cancer tissue could be detected by PET (Positron Emission Tomography) imaging. Selective detection and/or inhibition of HGF by HiP-8 is expected to be better diagnosis and/or therapeutics in drug discovery targeting HGF-MET.

[previous page]
The 59th KPSI Seminar　Morphological Superconductors: Fundamental discoveries in Superconducting Materials.
[next page]
The 61st KPSI Seminar　Dual-comb microscopy for scan-less confocal imaging