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 spec ifically 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 immunoreactiv e on the surfaces of most primary carcinomas and their metastases, whi le it is masked on normal cells. Tumor-specific surface carbohydrates are often used as markers of cell differentiation and play a role in c ell aggregation, which is an important step in the metastatic process. Therefore, peptides that bind and mask T antigen may yield useful car bohydrate-specific probes and provide insight into carbohydrate-mediat ed tumor-cell aggregation. A 15-amino acid random peptide bacteriophag e display library was screened for polypeptides that exhibited high sp ecificity to two glycoproteins which display T antigen on their surfac es. The results suggest that synthetic peptides identified from the ba cteriophage display library have high affinities (K-d similar to 1 mu M) 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 structur es.