Summary
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 ∼ 1 μM) 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.
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References
Hakomori, S.,Possible functions of tumor-associated carbohydrate antigens, Curr. Opin. Immunol., 3 (1991) 646–653.
Springer, G.F.,T and Tn: General carcinoma autoantigens, Science, 224 (1984) 1198–1206.
Hakomori, S.,Aberrant glycosylation in tumors and tumor-associated carbohydrate antigens, Adv. Cancer Res., 52 (1989) 257–331.
Springer, G.F. and Desai, P.R.,Extent of desialation of blood group MM, NN, and MN antigens for reactivity with human anti-T-antibody and Arachis hypogaea lectin, J. Biol. Chem., 257 (1982) 2744–2746.
Springer, G.F., Cheingsong-Popov, R., Schirrmacher, V., Desai, P.R. and Tegtmeyer, H.,Proposed molecular basis of murine tumor cell-hepatocyte interaction, J. Biol. Chem., 258 (1983) 5702–5706.
Glinsky, G.,Cell adhesion and metastasis: Is the site specificity of cancer metastasis determined by leukocyte-endothelial cell recognition and adhesion?, Crit. Rev. Oncol. Hematol., 14 (1993) 229–278.
Parmley, S.F. and Smith, G.P.,Antibody-selectable filamentous fd phage vectors: Affinity purification of target genes, Gene, 73 (1988) 305–318.
Smith, G.P. and Scott, J.K.,Libraries of proteins and peptides displayed on filamentous phage, Methods Enzymol., 217 (1993) 228–257.
Lotan, R., Skutelsky, E., Danon, D. and Sharon, N.,The purification, composition, and specificity of the anti-T-lectin from peanut (Arachis hypogaea), J. Biol. Chem., 250 (1975) 8518–8523.
Haas, S.J. and Smith, G.P.,Rapid screening of viral DNA from filamentous bacteriophage, Biotechniques, 15 (1993) 422–424.
Rutenber, E. and Robertus, J.D.,Structure of ricin B-chain at 2.5 Å resolution, Proteins, 10 (1991) 260–269.
Springer, T. and Lasky, L.,Sticky sugars for selectins, Nature, 349 (1991) 196–197.
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Peletskaya, E.N., Glinsky, G., Deutscher, S.L. et al. Identification of peptide sequences that bind the Thomsen-Friedenreich cancer-associated glycoantigen from bacteriophage peptide display libraries. Mol Divers 2, 13–18 (1996). https://doi.org/10.1007/BF01718695
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DOI: https://doi.org/10.1007/BF01718695