Partial D-amino acid substitution: Improved enzymatic stability and preserved Ab recognition of a MUC2 epitope peptide

Regina Tugyi, Katalin Uray, Dóra Iván, Erzsébet Fellinger, Alan Perkins, Ferenc Hudecz

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150 Citations (Scopus)


The stability of an immunogen against enzymatic degradation is considered an important factor for the design of synthetic vaccines. For our studies, we have selected an epitope from the tandem-repeat unit of the high-molecular- weight MUC2 mucin glycoprotein, which can be underglycosylated in case of colon cancer. In this study, we prepared a MUC2 peptide containing the PTGTQ epitope of a MUC2 protein backbone-specific mAb 996 and its derivatives. In these peptides, the N- and C-terminal flanking regions were systematically substituted by up to three D-amino acids. Peptides prepared by solid-phase synthesis were tested for their mAb 996 binding in competitive ELISA experiments, and their stability was studied in serum and lysosomal preparation. Our data show that the epitope function of peptide 15TPTPTGTQTPT25 is retained even in the presence of two D-amino acid residues at its N-terminal flanking region and up to three at its C-terminal flanking region (tpTPTGTQtpt). Also, this partly D peptide shows high resistance against proteolytic degradation in diluted human serum and in lysosomal preparation. These findings suggest that, by appropriate combination of structural modifications (namely, D-amino acid substitution) in the flanks of an Ab epitope, it is feasible to construct a synthetic antigen with preserved recognition properties and high stability against enzymatic degradation. Peptides tPTPTGTQTpt and tpTPTGTQTpt derived from this study can be used for immunization experiments and as potential components of synthetic vaccines for tumor therapy.

Original languageEnglish
Pages (from-to)413-418
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
Publication statusPublished - Jan 11 2005


  • Human serum
  • Rat liver lysosome preparation

ASJC Scopus subject areas

  • General

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