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The effect of the branched chain polypeptide carrier on biodistribution of covalently attached B-cell epitope peptide (APDTRPAPG) derived from mucin 1 glycoprotein

Author:
Uray, Katalin, Pimm, Malcolm V., Hudecz, Ferenc
Source:
Archives of biochemistry and biophysics 2019 v.664 pp. 127-133
ISSN:
0003-9861
Subject:
B-lymphocytes, amino acid composition, antibody formation, chemical bonding, epitopes, excretion, iodine, liver, mice, mucins, polymers, polypeptides, radiolabeling, spleen, structure-activity relationships, tissue distribution
Abstract:
In order to establish structure–function relationship for the design of a new group of oligopeptide antigen–macromolecule conjugate, multiple copies of mucin-1 B-cell epitope peptide, APDTRPAPG were conjugated with branched chain polymeric polypeptides possessing poly[L-Lys] backbone. By the synthesis, radiolabeling (125I) and in vivo treatment of BALB/c mice with epitope conjugates containing XiK/XAK type carrier, where X = Glu (EiK or EAK) or Leu (LAK), the influence of the polypeptide structure on the blood clearance profile and on tissue distribution profile concerning the epitope delivery to relevant organs (e.g. immunocompetent or involved in excretion) were investigated. We observed significant differences in the blood clearance profiles for the conjugates, the respective polypeptide carriers and free epitope peptide. All conjugates, regardless of their charge properties exhibited longer presence in the circulation than the free oligopeptide. Tissue distribution data also showed that the structural properties (e.g. amino acid composition, charge) of the carrier polypeptide have marked influence on the tissue accumulation of the epitope peptide conjugates. In contrast to conjugates with linear (K) or branched chain (LAK) polycationic polymers exhibiting rapid blood clearance and high spleen/liver uptake, amphoteric epitope peptide conjugates with different branches, but similar charge properties (EiK or EAK) had extended blood survival and generally lower tissue accumulation. The results on this systematic investigation suggest that further studies on the immune response induced by these epitope conjugates would be needed to provide correlation between biodistribution properties (presence in the blood, level of tissue accumulation) and the capacity of these conjugates to elicit antibody production.
Agid:
6306369