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


Autoria(s): Houimel M.; Schneider P.; Terskikh A.; Mach J.P.
Data(s)

2001

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_36C26829EA64

isbn:0020-7136 (Print)

pmid:11340582

doi:10.1002/1097-0215(20010601)92:5<748::AID-IJC1258>3.0.CO;2-1

isiid:000168420400021

Idioma(s)

en

Fonte

International Journal of Cancer, vol. 92, no. 5, pp. 748-755

Palavras-Chave #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
Tipo

info:eu-repo/semantics/article

article