Mucin structural interactions with an alginate oligomer mucolytic in cystic fibrosis sputum

Pritchard, Manon F. ORCID: https://orcid.org/0000-0002-5135-4744, Oakley, Juliette L., Brilliant, Charles D., Rye, Philip D., Forton, Julian ORCID: https://orcid.org/0000-0002-0580-0432, Doull, Iolo J. M., Ketchell, Ian, Hill, Katja E. ORCID: https://orcid.org/0000-0002-8590-0117, Thomas, David W. and Lewis, Paul D. 2019. Mucin structural interactions with an alginate oligomer mucolytic in cystic fibrosis sputum. Vibrational Spectroscopy 103 , 102932. 10.1016/j.vibspec.2019.102932

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Abstract

Cystic fibrosis (CF) is an autosomal recessive, life-limiting condition characterized by progressive lung disease, which is a major cause of morbidity and mortality for these patients. The inhalation therapy, OligoG CF-5/20, is a low molecular weight (mean Mn 3200 g/mol) alginate oligomer, with a high guluronic acid content (>85%). The ability of OligoG CF-5/20 to enhance the activity of antimicrobial/antibiotic therapies, modify the rheological properties of CF sputum and interact with mucin, has previously been shown. To further characterize the physicochemical interactions of OligoG CF-5/20 with CF sputum, Fourier-transform infrared (FTIR) spectroscopy was used to analyze ex vivo sputum samples from adolescent CF patients (n = 13) following treatment with 0.2% OligoG CF-5/20. FTIR analysis confirmed the interaction of OligoG CF-5/20 with mucin glycans in CF sputum, which showed a shift in wavenumber from 1078 cm−1 to 1070 cm-1 and subsequent loss of the 1053 cm−1 peak in the OligoG CF-5/20 treated samples. OligoG CF-5/20 interaction with key terminal moieties in mucin were also evident, with a significant change in sulphation at wavenumber 1116 cm−1, suggesting a link with sulphated Lewis x antigen. There were also significant shifts at wavenumber 1637 cm-1 indicative of β-sheet conformational changes in the mucin peptide caused by action of OligoG. The alterations in charge of glycan and mucin structures support previous observations wherein OligoG CF-5/20 modifies the viscoelastic properties of CF sputum. These findings suggest a possible mechanism of action for the rheological changes observed with this novel therapy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry Medicine
Publisher:	Elsevier
ISSN:	0924-2031
Date of First Compliant Deposit:	5 July 2019
Date of Acceptance:	11 June 2019
Last Modified:	29 Sep 2023 05:45
URI:	https://orca.cardiff.ac.uk/id/eprint/123903

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