RRC ID 44300
Author Iwata T, Tanaka K, Tahara T, Nozaki S, Onoe H, Watanabe Y, Fukase K.
Title A conformationally fixed analog of the peptide mimic Grb2-SH2 domain: synthesis and evaluation against the A431 cancer cell.
Journal Mol Biosyst
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.
Volume 9(5)
Pages 1019-25
Published 2013-5-1
DOI 10.1039/c3mb25462c
PMID 23403766
MeSH Animals Binding, Competitive Cell Line, Tumor Cell Survival / drug effects Chemistry Techniques, Synthetic Cyclization Dose-Response Relationship, Drug GRB2 Adaptor Protein / chemistry* GRB2 Adaptor Protein / metabolism Humans Mice Mice, Inbred BALB C Mice, Nude Models, Chemical Molecular Mimicry Molecular Structure Neoplasms / drug therapy Neoplasms / metabolism Neoplasms / pathology Peptides / chemical synthesis Peptides / chemistry* Peptides / pharmacology Peptides, Cyclic / chemistry Peptides, Cyclic / metabolism Peptides, Cyclic / pharmacology Phosphoproteins / chemistry Phosphoproteins / metabolism Protein Conformation* Xenograft Model Antitumor Assays src Homology Domains*
IF 2.855
Times Cited 4
Human and Animal Cells