A conformationally fixed analog of the peptide mimic Grb2-SH2 domain: Synthesis and evaluation against the A431 cancer cell

Takayuki Iwata, Katsunori Tanaka, Tsuyoshi Tahara, Satoshi Nozaki, Hirotaka Onoe, Yasuyoshi Watanabe, Koichi Fukase

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

A small peptide mimic of the Grb2-SH2 domain, which was previously prepared through the template-assisted click approach and exhibited selective A431 tumor growth inhibition both in vitro and in vivo, was further elaborated on to enhance the interaction with target phosphorylated proteins. A conformationally fixed analog was efficiently synthesized by solid-supported ring-closing metathesis and Cu(i)/His-mediated self-activating Huisgen [3+2] cycloadditon as the key steps, and exhibited a 10-fold enhanced affinity to a phosphorylated peptide, a truncated peptide analog of the Grb2-SH2-interacting phosphoproteins. A stronger interaction with the target phosphorylated proteins gave this cyclic analog cytotoxic activity in A431 cells.

Original languageEnglish
Pages (from-to)1019-1025
Number of pages7
JournalMolecular BioSystems
Volume9
Issue number5
DOIs
Publication statusPublished - May 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Biology

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