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

• DOI: 10.1016/j.vibspec.2019.102932
• Publication Date: 2019-06-12T11:45:26Z
• Authors: Manon F. Pritchard; Juliette L. Oakley; Charles D. Brilliant; Philip D. Rye; Julian Forton; Iolo J.M. Doull; Ian Ketchell; Katja E. Hill; David W. Thomas; Paul D. Lewis
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

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.