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

K. Uray, Malcolm V. Pimm, F. Hudecz

Research output: Article

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 ( 125 I) and in vivo treatment of BALB/c mice with epitope conjugates containing X i K/XAK type carrier, where X = Glu (E i K 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 (E i K 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.

Original languageEnglish
Pages (from-to)127-133
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume664
DOIs
Publication statusPublished - márc. 30 2019

Fingerprint

B-Lymphocyte Epitopes
Mucin-1
Glycoproteins
Epitopes
Peptides
Blood
Tissue
Oligopeptides
Tissue Distribution
Liver
Antibody Formation
Structural properties
Polymers
Spleen
Amino Acids
Antibodies

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

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title = "The effect of the branched chain polypeptide carrier on biodistribution of covalently attached B-cell epitope peptide (APDTRPAPG) derived from mucin 1 glycoprotein",
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 ( 125 I) and in vivo treatment of BALB/c mice with epitope conjugates containing X i K/XAK type carrier, where X = Glu (E i K 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 (E i K 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.",
keywords = "Biodistribution, Blood clearance – Conjugate structure relationship, Carrier effect, MUC-1 mucin peptide antigen, Oligopeptide epitope conjugates, Polymeric polypeptide carrier",
author = "K. Uray and Pimm, {Malcolm V.} and F. Hudecz",
year = "2019",
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doi = "10.1016/j.abb.2019.02.003",
language = "English",
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T1 - The effect of the branched chain polypeptide carrier on biodistribution of covalently attached B-cell epitope peptide (APDTRPAPG) derived from mucin 1 glycoprotein

AU - Uray, K.

AU - Pimm, Malcolm V.

AU - Hudecz, F.

PY - 2019/3/30

Y1 - 2019/3/30

N2 - 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 ( 125 I) and in vivo treatment of BALB/c mice with epitope conjugates containing X i K/XAK type carrier, where X = Glu (E i K 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 (E i K 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.

AB - 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 ( 125 I) and in vivo treatment of BALB/c mice with epitope conjugates containing X i K/XAK type carrier, where X = Glu (E i K 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 (E i K 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.

KW - Biodistribution

KW - Blood clearance – Conjugate structure relationship

KW - Carrier effect

KW - MUC-1 mucin peptide antigen

KW - Oligopeptide epitope conjugates

KW - Polymeric polypeptide carrier

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U2 - 10.1016/j.abb.2019.02.003

DO - 10.1016/j.abb.2019.02.003

M3 - Article

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VL - 664

SP - 127

EP - 133

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

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