Improvement of the enzymatic stability of a cytotoxic T-lymphocyte-epitope model peptide for its oral administration
| Autor: | A Otava, Michaela K. Marschütz, M Buschle, F Mattner, Andreas Bernkop-Schnürch, W Zauner |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Carboxypeptidases A
Physiology Swine Administration Oral Antigen-Presenting Cells Peptide Carboxypeptidases Biochemistry Intestinal absorption Epitope Cellular and Molecular Neuroscience Epitopes Leucyl Aminopeptidase Mice Endocrinology Drug Delivery Systems Antigen Intestinal mucosa Endopeptidases Enzyme Stability Animals Amino Acid Sequence Intestinal Mucosa Peptide sequence Cells Cultured chemistry.chemical_classification Drug Carriers biology Exopeptidase Carboxypeptidase Mice Inbred C57BL chemistry biology.protein Female Peptides T-Lymphocytes Cytotoxic |
| Zdroj: | Peptides. 23(10) |
| ISSN: | 0196-9781 |
| Popis: | Oral administration of peptide antigens, to provide proper mucosal and/or systemic immunity, is largely ineffective. This is mainly due to the very small quantity of antigen that survives degradation in the intestine and that crosses the intestinal absorption membrane. The present study focuses on the improvement of the enzymatic stability of a 13 amino acid long peptide containing a cytotoxic T-lymphocytes (CTL)-epitope. Within this study, it is shown, that simple chemical modification at the N- and C-terminus of the peptide can provide significant stability towards enzymatic attack by intestinal exopeptidases. Around 50% of the modified peptide resisted enzymatic attack on native porcine intestinal mucosa within 3h of incubation at pH 6.8 and 37 degrees C, whereas unmodified control peptide was almost completely degraded within the same time period. Additionally, a mucoadhesive drug carrier matrix with specific inhibitory properties towards luminally secreted endopeptidases has been generated. The incorporation of the simply modified peptide in this delivery system should enhance the amount of biologically active antigen being available at the mucosal site for further presentation to immunomodulating systems. This might open the door for a successful oral immunotherapy. |
| Databáze: | OpenAIRE |
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