دورية أكاديمية
Thiolated polyglycerol sulfate as potential mucolytic for muco-obstructive lung diseases.
| العنوان: | Thiolated polyglycerol sulfate as potential mucolytic for muco-obstructive lung diseases. |
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| المؤلفون: | Arenhoevel J; Freie Universität Berlin, Institute of Chemistry and Biochemistry, SupraFAB, Altensteinstr. 23a, 14195 Berlin, Germany. daniel.lauster@fu-berlin.de., Kuppe A; Charité - Universitätsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Augustenburger Platz 1, 13353 Berlin, Germany. marcus.mall@charite.de.; German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany., Addante A; Charité - Universitätsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Augustenburger Platz 1, 13353 Berlin, Germany. marcus.mall@charite.de.; German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany., Wei LF; Freie Universität Berlin, Institute of Chemistry and Biochemistry, SupraFAB, Altensteinstr. 23a, 14195 Berlin, Germany. daniel.lauster@fu-berlin.de.; Freie Universität Berlin, Institute of Pharmacy, Biopharmaceuticals, Kelchstraße 31, 12169 Berlin, Germany., Boback N; Freie Universität Berlin, Institute of Chemistry and Biochemistry, SupraFAB, Altensteinstr. 23a, 14195 Berlin, Germany. daniel.lauster@fu-berlin.de.; Freie Universität Berlin, Institute of Pharmacy, Biopharmaceuticals, Kelchstraße 31, 12169 Berlin, Germany., Butnarasu C; Freie Universität Berlin, Institute of Chemistry and Biochemistry, SupraFAB, Altensteinstr. 23a, 14195 Berlin, Germany. daniel.lauster@fu-berlin.de.; Freie Universität Berlin, Institute of Pharmacy, Biopharmaceuticals, Kelchstraße 31, 12169 Berlin, Germany., Zhong Y; Freie Universität Berlin, Institute of Chemistry and Biochemistry, SupraFAB, Altensteinstr. 23a, 14195 Berlin, Germany. daniel.lauster@fu-berlin.de., Wong C; Charité - Universitätsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Augustenburger Platz 1, 13353 Berlin, Germany. marcus.mall@charite.de.; German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany., Graeber SY; Charité - Universitätsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Augustenburger Platz 1, 13353 Berlin, Germany. marcus.mall@charite.de.; German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany.; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany., Duerr J; Charité - Universitätsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Augustenburger Platz 1, 13353 Berlin, Germany. marcus.mall@charite.de.; German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany., Gradzielski M; Technische Universität Berlin, Institute of Chemistry, Straße des 17. Juni 124, 10623 Berlin, Germany., Lauster D; Freie Universität Berlin, Institute of Chemistry and Biochemistry, SupraFAB, Altensteinstr. 23a, 14195 Berlin, Germany. daniel.lauster@fu-berlin.de.; Freie Universität Berlin, Institute of Pharmacy, Biopharmaceuticals, Kelchstraße 31, 12169 Berlin, Germany., Mall MA; Charité - Universitätsmedizin Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Augustenburger Platz 1, 13353 Berlin, Germany. marcus.mall@charite.de.; German Center for Lung Research (DZL), Associated Partner Site, 13353 Berlin, Germany.; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany., Haag R; Freie Universität Berlin, Institute of Chemistry and Biochemistry, SupraFAB, Altensteinstr. 23a, 14195 Berlin, Germany. daniel.lauster@fu-berlin.de. |
| المصدر: | Biomaterials science [Biomater Sci] 2024 Aug 20; Vol. 12 (17), pp. 4376-4385. Date of Electronic Publication: 2024 Aug 20. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101593571 Publication Model: Electronic Cited Medium: Internet ISSN: 2047-4849 (Electronic) Linking ISSN: 20474830 NLM ISO Abbreviation: Biomater Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, UK : Royal Society of Chemistry |
| مواضيع طبية MeSH: | Glycerol*/chemistry , Polymers*/chemistry , Polymers*/pharmacology , Sputum*/metabolism , Sputum*/chemistry , Sulfhydryl Compounds*/chemistry , Sulfhydryl Compounds*/pharmacology, Humans ; Cystic Fibrosis/metabolism ; Cystic Fibrosis/drug therapy ; Mucin 5AC/metabolism ; Lung Diseases, Obstructive/drug therapy ; Lung Diseases, Obstructive/metabolism ; Mucin-5B/metabolism ; Sulfates/chemistry ; Sulfates/pharmacology ; Expectorants/pharmacology ; Expectorants/chemistry ; Mucus/metabolism ; Mucus/chemistry ; Rheology ; Acetylcysteine/pharmacology ; Acetylcysteine/chemistry ; Viscosity |
| مستخلص: | Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale. After a physicochemical compound characterization, we compare the mucolytic activity of dPGS-SH to the clinically approved N -acetylcysteine (NAC) using western blot studies and investigate the effect of dPGS-SH on the viscoelastic properties of sputum samples from CF patients by oscillatory rheology. We show that dPGS-SH is more effective than NAC in reducing multimer intensity of the secreted mucins MUC5B and MUC5AC and demonstrate significant mucolytic activity by rheology. In addition, we provide data for dPGS-SH demonstrating a high compound stability, low cytotoxicity, and superior reaction kinetics over NAC at different pH levels. Our data support further development of the novel reducing polymer system dPGS-SH as a potential mucolytic to improve mucus function and clearance in patients with CF as well as other muco-obstructive lung diseases. |
| المشرفين على المادة: | 25618-55-7 (polyglycerol) PDC6A3C0OX (Glycerol) 0 (Polymers) 0 (Sulfhydryl Compounds) 0 (Mucin 5AC) 0 (MUC5AC protein, human) 0 (Mucin-5B) 0 (Sulfates) 0 (Expectorants) WYQ7N0BPYC (Acetylcysteine) 0 (MUC5B protein, human) |
| تواريخ الأحداث: | Date Created: 20240719 Date Completed: 20240820 Latest Revision: 20240820 |
| رمز التحديث: | 20240820 |
| DOI: | 10.1039/d4bm00381k |
| PMID: | 39028033 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2047-4849 |
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| DOI: | 10.1039/d4bm00381k |