Identification and characterization of peptides that bind human ErbB-2 selected from a bacteriophage display library.
The ErbB-2 receptor, a member of the tyrosine kinase type 1 family of receptors, has been implicated in many human malignancies. The overexpression of ErbB-2 in cancer cells as well as its extracellular accessibility makes it an attractive target for the development of tumor-specific agents. In this study, random peptide bacteriophage display technology was employed to identify peptides that bound the extracellular domain of human ErbB-2. The peptide KCCYSL, most frequently occurring in the affinity-selected phage population, was chemically synthesized and characterized for its binding activities to ErbB-2. The synthetic peptide exhibited high specificity for ErbB-2 and an equilibrium dissociation constant of 30 microM. Peptide binding to ErbB-2 positive human breast and prostate carcinoma cells was visualized in direct cell binding assays. In conclusion, the peptide KCCYSL has the potential to be developed into a cancer imaging or therapeutic agent targeting malignant cells overexpressing the ErbB-2 receptor.
Karasseva
Natalia G
NG
Department of Biochemistry, University of Missouri, Columbia, 65211, USA.
Glinsky
Vladislav V
VV
Chen
Ning X
NX
Komatireddy
Ravichandra
R
Quinn
Thomas P
TP
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics*; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004815:Epidermal Growth Factor; D009363:Neoplasm Proteins; D019151:Peptide Library; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases