Selection of peptides and synthesis of pentameric peptabody molecules reacting specifically with ErbB-2 receptor.

Details

Serval ID
serval:BIB_36C26829EA64
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Selection of peptides and synthesis of pentameric peptabody molecules reacting specifically with ErbB-2 receptor.
Journal
International Journal of Cancer
Author(s)
Houimel M., Schneider P., Terskikh A., Mach J.P.
ISSN
0020-7136 (Print)
ISSN-L
0020-7136
Publication state
Published
Issued date
2001
Volume
92
Number
5
Pages
748-755
Language
english
Abstract
The HER-2/ErbB-2 oncoprotein is overexpressed in human breast and ovarian adenocarcinomas and is clearly associated with the malignant phenotype. Although no specific ligand for this receptor has been positively identified, ErbB-2 was shown to play a central role in a network of interactions with the related ErbB-1, ErbB-3 and ErbB-4 receptors. We have selected new peptides binding to ErbB-2 extracellular domain protein (ECD) by screening 2 newly developed constrained and unconstrained random hexapeptide phage libraries. Out of 37 phage clones, which bound specifically to ErbB-2 ECD, we found 6 constrained and 10 linear different hexapeptide sequences. Among the latter, 5 consensus motifs, all with a common methionine and a positively charged residue at positions 1 and 3, respectively, were identified. Furthermore, 3 representative hexapeptides were fused to a coiled-coil pentameric recombinant protein to form the so-called peptabodies recently developed in our laboratory. The 3 peptabodies bound specifically to the ErbB-2 ECD, as determined by enzyme-linked immunosorbent assay and BIAcore analysis and to tumor cells overexpressing ErbB-2, as shown by flow cytometry. Interestingly, one of the free selected linear peptides and all 3 peptabodies inhibited the proliferation of tumor cells overexpressing ErbB-2. In conclusion, a novel type of ErbB-2-specific ligand is described that might complement presently available monoclonal antibodies.
Keywords
Amino Acid Sequence, Antibodies, Monoclonal/therapeutic use, Antineoplastic Agents/metabolism, Female, Humans, Molecular Sequence Data, Oligopeptides/metabolism, Peptide Library, Receptor, erbB-2/metabolism, Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 18:31
Last modification date
20/08/2019 14:24
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