Monoclonal antibody binding to peptide epitopes conjugated to synthetic branched chain polypeptide carriers. Influence of the carrier upon antibody recognition.
The peptide C A P D T R P A P G has been linked covalently to defined branched polypeptides with a polylysine backbone and side chains of DL-alanine or D-leucine-DL-alanine oligopeptides. The peptide was coupled via its N terminal cysteine to the side chains of the macromolecular carrier to ensure uniform orientation. The compounds were subjected to compositional analyses to characterise the degrees of substitution and secondary structural studies were performed using circular dichroism spectroscopy. The peptide selected for investigation contains the immunodominant sequence P D T R P A P which is expressed in the protein core of epithelial mucins. It is to this region that many anti-mucin monoclonal antibodies bind (Burchell et al., 1989; Price et al., 1990a,b). With these characterised constructs, it has been possible to evaluate the influence of secondary structure upon the binding of monoclonal antibodies which recognise short linear sequences in the synthetic antigenic peptide. The findings are relevant to the design and construction of synthetic immunogens and vaccines as well as to the production of synthetic analogues of clinically relevant antigens (in this case, epithelial mucins associated with breast and ovarian carcinomas).
Research Group of Peptide Chemistry, Hungarian Academy of Science, Eötvös L. University, Budapest.
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D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D002942:Circular Dichroism; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009077:Mucins / Q000276:immunology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D000939:Epitopes; D016056:Immunodominant Epitopes; D009077:Mucins; D009842:Oligopeptides; D010455:Peptides; C057387:mucinous carcinoma-associated antigen