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OligoG CF-5/20 normalizes cystic fibrosis mucus by chelating calcium.

Journal article
Authors Anna Ermund
Christian V Recktenwald
Gudmund Skjåk-Braek
Lauren N Meiss
Edvar Onsøyen
Philip D Rye
Arne Dessen
Astrid Hilde Myrset
Gunnar C. Hansson
Published in Clinical and experimental pharmacology & physiology
Volume 44
Issue 6
Pages 639–647
ISSN 1440-1681
Publication year 2017
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 639–647
Language en
Links dx.doi.org/10.1111/1440-1681.12744
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cell and Molecular Biology, Pharmaceutical Sciences, Pharmaceutical biochemistry

Abstract

The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF-5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N-terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis. Further, effects on mucus thickness and attachment induced by OligoG and other alginate fractions of different length and composition were evaluated in explants of CF mouse ileum mounted in horizontal Ussing-type chambers. OligoG at 1.5% caused effective detachment of CF mucus and the most potent alginate fraction tested, the poly-G fraction of about 12 residues, had similar potency compared to OligoG whereas mannuronate-rich (M) polymers had minimal effect. In conclusion, OligoG binds calcium with appropriate affinity without any overt harmful effect on the tissue and can be exploited for treating mucus stagnation. This article is protected by copyright. All rights reserved.

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