Identification and Characterization of MUC5B Binding Peptides by Phage Display

Autor: Mouri R.J. Faruque, Nivedita Cukkemane, Cuicui Fu, Kamran Nazmi, Marja L. Laine, Floris J. Bikker
Přispěvatelé: Oral Biochemistry, Academic Centre for Dentistry Amsterdam, Periodontology
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Faruque, M R J, Cukkemane, N, Fu, C, Nazmi, K, Laine, M L & Bikker, F J 2023, ' Identification and Characterization of MUC5B Binding Peptides by Phage Display ', Archives of Oral Biology, vol. 147, 105624, pp. 1-8 . https://doi.org/10.1016/j.archoralbio.2023.105624
Archives of Oral Biology, 147:105624, 1-8. Elsevier Limited
ISSN: 0003-9969
DOI: 10.1016/j.archoralbio.2023.105624
Popis: Objectives: MUC5B plays a multifactorial role in oral health. As a consequence, decreased MUC5B output leads to impaired salivary functions and xerostomia. Synthetic combinatorial technologies have been used to develop functional peptide libraries by phage display e.g. for therapeutic purposes. In this light, our primary aim was to identify peptide sequences with specific selectivity for salivary MUC5B in vitro using phage display. Our secondary aims were to analyze their effect on salivary spinnbarkeit in situ and their effect on acid-induced demineralization in vitro. Methods: MUC5B binding phages were selected by phage display. Peptide affinity to MUC5B was evaluated using MUC5B coated hydroxyapatite (HA) granules. The MUC5B binding peptides (MBPs) were then examined for their effects on salivary spinnbarkeit and protective effect on acid-induced demineralization in vitro. A competitive ELISA was performed to identify the binding epitope on MUC5B using F2, a MUC5B specific antibody. Results: MBP-12 and MBP-14 displayed the highest affinity to MUC5B. MBP-12 mildly stabilized the spinnbarkeit of serous saliva after overnight incubation and of mucous saliva at all timepoints tested. The addition of MBP-12 to a pellicle of unstimulated saliva on HA discs showed no additive protective effect against acid-induced demineralization. Epitope characterization suggested sulfo-Lewisa SO3–3Gal_1–3GlcNAc (galactose residue) as MBP-12 binding site on MUC5B. Conclusions: The use of phage display in generating MBPs was successful. Characterization of the MBPs revealed a mild effect on spinnbarkeit in case of mucous saliva. Possibly, combinatorial peptide libraries might contribute to the development of novel formulations to treat xerostomia.
Databáze: OpenAIRE
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