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Macrocyclic peptide-based inhibition and imaging of hepatocyte growth factor.
Sakai, Katsuya; Passioura, Toby; Sato, Hiroki; Ito, Kenichiro; Furuhashi, Hiroki; Umitsu, Masataka; Takagi, Junichi; Kato, Yukinari; Mukai, Hidefumi; Warashina, Shota; Zouda, Maki; Watanabe, Yasuyoshi; Yano, Seiji; Shibata, Mikihiro; Suga, Hiroaki; Matsumoto, Kunio.
Afiliação
  • Sakai K; Division of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
  • Passioura T; WPI-Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
  • Sato H; Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Ito K; Sydney Analytical, The University of Sydney, Sydney New, South Wales, Australia.
  • Furuhashi H; Division of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
  • Umitsu M; WPI-Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
  • Takagi J; Department of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Kato Y; Mathematical and Physical Sciences, Graduate School of Natural Science & Technology, Kanazawa University, Kanazawa, Japan.
  • Mukai H; Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.
  • Warashina S; Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.
  • Zouda M; Medicine/New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan.
  • Watanabe Y; Laboratory for Molecular Delivery and Imaging Technology, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
  • Yano S; Laboratory for Molecular Delivery and Imaging Technology, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
  • Shibata M; Laboratory for Molecular Delivery and Imaging Technology, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
  • Suga H; Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
  • Matsumoto K; WPI-Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
Nat Chem Biol ; 15(6): 598-606, 2019 06.
Article em En | MEDLINE | ID: mdl-31101918
Activation of hepatocyte growth factor (HGF) by proteolytic processing is triggered in cancer microenvironments, and subsequent signaling through the MET receptor is involved in cancer progression. However, the structure of HGF remains elusive, and few small/medium-sized molecules can modulate HGF. Here, we identified HiP-8, a macrocyclic peptide consisting of 12 amino acids, which selectively recognizes active HGF. Biochemical analysis and real-time single-molecule imaging by high-speed atomic force microscopy demonstrated that HiP-8 restricted the dynamic domains of HGF into static closed conformations, resulting in allosteric inhibition. Positron emission tomography using HiP-8 as a radiotracer enabled noninvasive visualization and simultaneous inhibition of HGF-MET activation status in tumors in a mouse model. Our results illustrate the conformational change in proteolytic activation of HGF and its detection and inhibition by a macrocyclic peptide, which may be useful for diagnosis and treatment of cancers.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos / Fator de Crescimento de Hepatócito / Compostos Macrocíclicos / Imagem Óptica / Neoplasias Experimentais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Chem Biol Assunto da revista: BIOLOGIA / QUIMICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Japão País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos / Fator de Crescimento de Hepatócito / Compostos Macrocíclicos / Imagem Óptica / Neoplasias Experimentais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Nat Chem Biol Assunto da revista: BIOLOGIA / QUIMICA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Japão País de publicação: Estados Unidos