Identification of peptide sequences that bind the Thomsen-Friedenreich cancer-associated glycoantigen from bacteriophage peptide display libraries.
The goal of this study was to determine if polypeptides that bind specifically to the carcinoma-associated Thomsen-Friedenreich (T) antigen could be isolated from a random peptide bacteriophage display library. T antigen is a carbohydrate antigen that is exposed and immunoreactive on the surfaces of most primary carcinomas and their metastases, while it is masked on normal cells. Tumor-specific surface carbohydrates are often used as markers of cell differentiation and play a role in cell aggregation, which is an important step in the metastatic process. Therefore, peptides that bind and mask T antigen may yield useful carbohydrate-specific probes and provide insight into carbohydrate-mediated tumor-cell aggregation. A 15-amino acid random peptide bacteriophage display library was screened for polypeptides that exhibited high specificity to two glycoproteins which display T antigen on their surfaces. The results suggest that synthetic peptides identified from the bacteriophage display library have high affinities (Kd approximately 1 microM) and specificities for proteins and human tumor cells which present T antigen. Thus, random bacteriophage peptide display libraries may be a rich source of sequences that bind to carbohydrate antigen structures.
Peletskaya
E N
EN
Department of Biochemistry, University of Missouri, Columbia 65211, USA.
Glinsky
G
G
Deutscher
S L
SL
Quinn
T P
TP
D000595:Amino Acid Sequence; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D002277:Carcinoma; D003110:Colonic Neoplasms; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes; D006801:Humans; D017911:Inoviridae / Q000302:isolation & purification / Q000378:metabolism*; D008545:Melanoma; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015295:Antigens, Tumor-Associated, Carbohydrate; D005456:Fluorescent Dyes; D019151:Peptide Library; D010455:Peptides; C040286:Tn antigen