Efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography
Pulmonary surfactant preparations extracted from natural sources have been used to treat millions of newborn babies with respiratory distress syndrome (RDS) and can possibly also be used to treat other lung diseases. Due to costly production and limited supply of animal-derived surfactants, syntheti...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892477/ https://www.ncbi.nlm.nih.gov/pubmed/31800629 http://dx.doi.org/10.1371/journal.pone.0226072 |
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author | Basabe-Burgos, Oihana Ahlström, Jakub Zebialowicz Mikolka, Pavol Landreh, Michael Johansson, Jan Curstedt, Tore Rising, Anna |
author_facet | Basabe-Burgos, Oihana Ahlström, Jakub Zebialowicz Mikolka, Pavol Landreh, Michael Johansson, Jan Curstedt, Tore Rising, Anna |
author_sort | Basabe-Burgos, Oihana |
collection | PubMed |
description | Pulmonary surfactant preparations extracted from natural sources have been used to treat millions of newborn babies with respiratory distress syndrome (RDS) and can possibly also be used to treat other lung diseases. Due to costly production and limited supply of animal-derived surfactants, synthetic alternatives are attractive. The water insolubility and aggregation-prone nature of the proteins present in animal-derived surfactant preparations have complicated development of artificial surfactant. A non-aggregating analog of lung surfactant protein C, SP-C33Leu is used in synthetic surfactant and we recently described an efficient method to produce rSP-C33Leu in bacteria. Here rSP-C33Leu obtained by salt precipitation of bacterial extracts was purified by two-step liquid gel chromatography and analyzed using mass spectrometry and RP-HPLC, showing that it is void of modifications and adducts. Premature New Zealand White rabbit fetuses instilled with 200mg/kg of 2% of rSP-C33Leu in phospholipids and ventilated with a positive end expiratory pressure showed increased tidal volumes and lung gas volumes compared to animals treated with phospholipids only. This shows that rSP-C33Leu can be purified from bacterial lipids and that rSP-C33Leu surfactant is active against experimental RDS. |
format | Online Article Text |
id | pubmed-6892477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-68924772019-12-14 Efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography Basabe-Burgos, Oihana Ahlström, Jakub Zebialowicz Mikolka, Pavol Landreh, Michael Johansson, Jan Curstedt, Tore Rising, Anna PLoS One Research Article Pulmonary surfactant preparations extracted from natural sources have been used to treat millions of newborn babies with respiratory distress syndrome (RDS) and can possibly also be used to treat other lung diseases. Due to costly production and limited supply of animal-derived surfactants, synthetic alternatives are attractive. The water insolubility and aggregation-prone nature of the proteins present in animal-derived surfactant preparations have complicated development of artificial surfactant. A non-aggregating analog of lung surfactant protein C, SP-C33Leu is used in synthetic surfactant and we recently described an efficient method to produce rSP-C33Leu in bacteria. Here rSP-C33Leu obtained by salt precipitation of bacterial extracts was purified by two-step liquid gel chromatography and analyzed using mass spectrometry and RP-HPLC, showing that it is void of modifications and adducts. Premature New Zealand White rabbit fetuses instilled with 200mg/kg of 2% of rSP-C33Leu in phospholipids and ventilated with a positive end expiratory pressure showed increased tidal volumes and lung gas volumes compared to animals treated with phospholipids only. This shows that rSP-C33Leu can be purified from bacterial lipids and that rSP-C33Leu surfactant is active against experimental RDS. Public Library of Science 2019-12-04 /pmc/articles/PMC6892477/ /pubmed/31800629 http://dx.doi.org/10.1371/journal.pone.0226072 Text en © 2019 Basabe-Burgos et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Basabe-Burgos, Oihana Ahlström, Jakub Zebialowicz Mikolka, Pavol Landreh, Michael Johansson, Jan Curstedt, Tore Rising, Anna Efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography |
title | Efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography |
title_full | Efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography |
title_fullStr | Efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography |
title_full_unstemmed | Efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography |
title_short | Efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography |
title_sort | efficient delipidation of a recombinant lung surfactant lipopeptide analogue by liquid-gel chromatography |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892477/ https://www.ncbi.nlm.nih.gov/pubmed/31800629 http://dx.doi.org/10.1371/journal.pone.0226072 |
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