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Improvement of the enzymatic stability of a cytotoxic T-lymphocyte-epitope model peptide for its oral administration
Abstract
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.
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Metadata
- Authors
- Marschütz, M. K., Zauner, W., Mattner, F., Otava, A., Buschle, M., & Bernkop-Schnürch, A.
- Affiliations
- University of Vienna (AT)
- Intercell (Austria) (AT)
- Venue
- Peptides
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 23
- Issue
- 10
- Pages
- 1727-1733
- ISSN
- 0196-9781 (ISSN-L)
- OpenAlex
- W2084914681
- Cited by
- 24
- References
- 23
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2018: 1 · 2017: 1 · 2015: 2 · 2014: 5
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Peptides (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CTL epitopes, oral immunotherapy, oral antigen delivery, peptide modification, porcine intestinal mucosa, endopeptidase inhibition, mucosal immunity, peptide degradation
- MeSH terms
- Administration, Oral, Amino Acid Sequence, Animals, Antigen-Presenting Cells, Epitopes, Carboxypeptidases, Cells, Cultured, Drug Carriers, Enzyme Stability, Female, Intestinal Mucosa, Leucyl Aminopeptidase, Mice, Inbred C57BL, Endopeptidases, Peptides, Swine, T-Lymphocytes, Cytotoxic, Drug Delivery Systems, Carboxypeptidases A, Mice
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