Synthesis of glycophospholipid conjugates with mono- and disaccharides by enzymatic transphosphatidylation
Barchan, Nikolina LU and Adlercreutz, Patrick LU
(2024)
In European Journal of Lipid Science and Technology
126(3).
- Abstract
Phospholipids, PLs, are interesting and highly abundant amphiphilic molecules, which self-assemble into 3D nanostructures that have big interest as formulation excipients in, for example, pharma industry. However, the structures that are formed by naturally occurring PLs usually suffer from rigidity problems, and the nanostructures have to be modified in various ways for improved stability. One such approach is by the conjugation of saccharides to the PL head group. In this study, we investigate reaction conditions for the scalable phospholipase D–catalyzed transphosphatidylation reaction for the synthesis of glycophospholipids. Biphasic reaction systems with different solvents are compared with a purely aqueous system with PLs... (More)
Phospholipids, PLs, are interesting and highly abundant amphiphilic molecules, which self-assemble into 3D nanostructures that have big interest as formulation excipients in, for example, pharma industry. However, the structures that are formed by naturally occurring PLs usually suffer from rigidity problems, and the nanostructures have to be modified in various ways for improved stability. One such approach is by the conjugation of saccharides to the PL head group. In this study, we investigate reaction conditions for the scalable phospholipase D–catalyzed transphosphatidylation reaction for the synthesis of glycophospholipids. Biphasic reaction systems with different solvents are compared with a purely aqueous system with PLs dispersed as vesicles. The investigations showed that use of the biphasic system containing chloroform and a glucose/phosphatidylcholine ratio of 50, in combination with carefully selected enzyme concentration and reaction time, led to an optimized process without any hydrolytic side reaction for the synthesis of phosphatidyl glucose. The reaction system was then applied to a variety of different mono- and disaccharides for the synthesis of a range of different glycophospholipids, resulting in yields up to 85% of phosphatidyl monosaccharides and 35% of disaccharides. Practical Application: Phospholipids and other polar lipids are of great scientific interest as formulation excipients. The chemical structures of lipids used for such applications have major impact on the properties of the self-aggregated systems. Synthesis of new phospholipids with modified head groups can tremendously widen the portfolio of available choices of formulation excipients and make it possible to make customized formulations with the desired properties. The introduction of saccharides in the hydrophilic part of the phospholipid alters the chemistry of head group and its interaction with surrounding water in vesicle systems and should therefore have a significant effect on its formulating properties compared to natural phospholipids.
(Less)
- author
- Barchan, Nikolina
LU
and Adlercreutz, Patrick
LU
- organization
- publishing date
- 2024-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- glycophospholipids, phosphatidyl glucose, phosphatidyl saccharide, phospholipase D, transphosphatidylation
- in
- European Journal of Lipid Science and Technology
- volume
- 126
- issue
- 3
- article number
- 2300240
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85184218078
- ISSN
- 1438-7697
- DOI
- 10.1002/ejlt.202300240
- language
- English
- LU publication?
- yes
- id
- 4eda9c22-44a3-462d-b901-5579a6692f75
- date added to LUP
- 2024-03-11 12:42:24
- date last changed
- 2024-03-19 10:20:33
@article{4eda9c22-44a3-462d-b901-5579a6692f75,
abstract = {{<p>Phospholipids, PLs, are interesting and highly abundant amphiphilic molecules, which self-assemble into 3D nanostructures that have big interest as formulation excipients in, for example, pharma industry. However, the structures that are formed by naturally occurring PLs usually suffer from rigidity problems, and the nanostructures have to be modified in various ways for improved stability. One such approach is by the conjugation of saccharides to the PL head group. In this study, we investigate reaction conditions for the scalable phospholipase D–catalyzed transphosphatidylation reaction for the synthesis of glycophospholipids. Biphasic reaction systems with different solvents are compared with a purely aqueous system with PLs dispersed as vesicles. The investigations showed that use of the biphasic system containing chloroform and a glucose/phosphatidylcholine ratio of 50, in combination with carefully selected enzyme concentration and reaction time, led to an optimized process without any hydrolytic side reaction for the synthesis of phosphatidyl glucose. The reaction system was then applied to a variety of different mono- and disaccharides for the synthesis of a range of different glycophospholipids, resulting in yields up to 85% of phosphatidyl monosaccharides and 35% of disaccharides. Practical Application: Phospholipids and other polar lipids are of great scientific interest as formulation excipients. The chemical structures of lipids used for such applications have major impact on the properties of the self-aggregated systems. Synthesis of new phospholipids with modified head groups can tremendously widen the portfolio of available choices of formulation excipients and make it possible to make customized formulations with the desired properties. The introduction of saccharides in the hydrophilic part of the phospholipid alters the chemistry of head group and its interaction with surrounding water in vesicle systems and should therefore have a significant effect on its formulating properties compared to natural phospholipids.</p>}},
author = {{Barchan, Nikolina and Adlercreutz, Patrick}},
issn = {{1438-7697}},
keywords = {{glycophospholipids; phosphatidyl glucose; phosphatidyl saccharide; phospholipase D; transphosphatidylation}},
language = {{eng}},
number = {{3}},
publisher = {{John Wiley & Sons Inc.}},
series = {{European Journal of Lipid Science and Technology}},
title = {{Synthesis of glycophospholipid conjugates with mono- and disaccharides by enzymatic transphosphatidylation}},
url = {{http://dx.doi.org/10.1002/ejlt.202300240}},
doi = {{10.1002/ejlt.202300240}},
volume = {{126}},
year = {{2024}},
}