RRC ID 62784
Author Toyama K, Mizuguchi T, Nomura W, Tamamura H.
Title Functional evaluation of fluorescein-labeled derivatives of a peptide inhibitor of the EGF receptor dimerization.
Journal Bioorg Med Chem
Abstract A cyclic decapeptide (1, ), which acts on the extracellular region of the EGF receptor, preventing it from dimerizing, has been developed. Peptide 2, which was labeled with fluorescein at the N-terminus of peptide 1, was synthesized based on structure-activity relationship studies. Peptide 2 essentially retained the inhibitory activity of peptide 1 against the receptor autophosphorylation. Confocal microscopy studies revealed that in carcinoma cells, the fluorescence of peptide 2 was localized inside some vesicles. Treatment of intact cells by peptide 1 in combination with peptide 2 decreased the fluorescence intensity significantly compared to treatment with only peptide 2. These results indicate that peptide 2 competes with peptide 1 for binding to the cellular surface. Six derivatives of peptide 2, in which constituent amino acids, with the exception of two cysteines and proline were randomized, were synthesized and used to treat the cells. Peptides 6 and 9 showed the highest fluorescence intensity in cells. From the results of the EGF receptor autophosphorylation assay, these two derivatives were proven to have higher inhibitory activity than peptide 2, which would therefore be a useful delivery peptide and fluorescent probe to find new inhibitors against the EGF receptor. Peptides 6 and 9 are promising leads for EGF receptor inhibitors.
Volume 24(16)
Pages 3406-12
Published 2016-8-15
DOI 10.1016/j.bmc.2016.05.026
PII S0968-0896(16)30350-9
PMID 27283787
MeSH Amino Acid Sequence Cell Line, Tumor Chromatography, High Pressure Liquid Dimerization ErbB Receptors / metabolism* Fluorescein / chemistry* Humans Peptides / chemistry Peptides / pharmacology* Spectrometry, Mass, Electrospray Ionization
IF 3.073
Human and Animal Cells A431(RCB0202) A549(RCB0098)