Novel glycophospholipids: : Phospholipase D catalysed synthesis and characterization
(2025)- Abstract
- Phospholipids are amphiphilic molecules that self-assemble into organized structures such as bilayers and vesicles when dispersed in aqueous solutions. This property in addition to their biocompatibility, biodegradability, and natural abundance in high titres makes phospholipids highly attractive as formulation excipients for a wide range of biological and technical applications. However, isolating phospholipids other than the commonly occurring phosphatidylcholine is challenging, particularly concerning the hydrophobic tails that often come in a variety of lengths and degree of unsaturation. This can be limiting in their use in technically advanced formulations that demand precise and reproducible chemical specifications. To address this,... (More)
- Phospholipids are amphiphilic molecules that self-assemble into organized structures such as bilayers and vesicles when dispersed in aqueous solutions. This property in addition to their biocompatibility, biodegradability, and natural abundance in high titres makes phospholipids highly attractive as formulation excipients for a wide range of biological and technical applications. However, isolating phospholipids other than the commonly occurring phosphatidylcholine is challenging, particularly concerning the hydrophobic tails that often come in a variety of lengths and degree of unsaturation. This can be limiting in their use in technically advanced formulations that demand precise and reproducible chemical specifications. To address this, the modification of phospholipid head groups has emerged as a valuable strategy, not only for enriching natural phospholipids but also for introducing novel functionalities with tailored properties. Such modifications has the potential to enable refined formulations with enhanced characteristics including improved drug delivery, higher encapsulation efficiency of pharmaceutical ingredients, and better colloidal stability.
In this thesis, we investigate the structural modification of phospholipid head groups through the conjugation of small carbohydrates. Using a phospholipase D (PLD)-catalysed transphosphati-dylation reaction, we successfully conjugated various carbohydrates to the phospholipid head group. The resulting glycophospholipid conjugates were characterized for their self-assembly behaviour using small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). Our findings reveal that head group modifications have a profound impact on lipid self-assembly. The type of carbohydrate in the head group significantly influenced vesicle structures, resulting in variations in size and lamellarity. Small changes in the orientation of hydroxyl groups, as dictated by different carbohydrates, induced substantial differences in vesicle morphology. The use of PLD catalyzed enzymatic transphosphatidylation represents a powerful strategy for synthesis of novel glycophospholipid materials, which are otherwise difficult to achieve through traditional synthetic methods. By harnessing the complex nature and structurally rich diversity of carbohydrates, this approach enables the synthesis of an extensive variety of glycophospholipid conjugates with distinct properties. This work demonstrates an effective method for designing advanced lipid-based materials tailored for diverse applications such as drug delivery, nanotechnology, and biomedicine, where precise control of self-assembly and functionality is essential.
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Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/979ac790-261e-49ab-abba-dc6d31673785
- author
- Barchan, Nikolina LU
- supervisor
- opponent
-
- Assoc. Prof. D’Arrigo, Paola, Politecnico di Milano, Italy.
- organization
- publishing date
- 2025
- type
- Thesis
- publication status
- published
- subject
- keywords
- phospholipid, carbohydrate, transphosphatidylation, phospholipase D, lipid self-assembly, polar lipid
- pages
- 66 pages
- publisher
- Department of Biotechnology, Lund University
- defense location
- Lecture Hall KC:A, Kemicentrum, Naturvetarvägen 22, Faculty of Engineering LTH, Lund University, Lund.
- defense date
- 2025-06-05 09:15:00
- ISBN
- 978-91-8096-108-0
- 978-91-8096-109-7
- language
- English
- LU publication?
- yes
- id
- 979ac790-261e-49ab-abba-dc6d31673785
- date added to LUP
- 2025-05-06 09:03:54
- date last changed
- 2025-05-07 11:15:57
@phdthesis{979ac790-261e-49ab-abba-dc6d31673785,
abstract = {{Phospholipids are amphiphilic molecules that self-assemble into organized structures such as bilayers and vesicles when dispersed in aqueous solutions. This property in addition to their biocompatibility, biodegradability, and natural abundance in high titres makes phospholipids highly attractive as formulation excipients for a wide range of biological and technical applications. However, isolating phospholipids other than the commonly occurring phosphatidylcholine is challenging, particularly concerning the hydrophobic tails that often come in a variety of lengths and degree of unsaturation. This can be limiting in their use in technically advanced formulations that demand precise and reproducible chemical specifications. To address this, the modification of phospholipid head groups has emerged as a valuable strategy, not only for enriching natural phospholipids but also for introducing novel functionalities with tailored properties. Such modifications has the potential to enable refined formulations with enhanced characteristics including improved drug delivery, higher encapsulation efficiency of pharmaceutical ingredients, and better colloidal stability.<br/>In this thesis, we investigate the structural modification of phospholipid head groups through the conjugation of small carbohydrates. Using a phospholipase D (PLD)-catalysed transphosphati-dylation reaction, we successfully conjugated various carbohydrates to the phospholipid head group. The resulting glycophospholipid conjugates were characterized for their self-assembly behaviour using small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). Our findings reveal that head group modifications have a profound impact on lipid self-assembly. The type of carbohydrate in the head group significantly influenced vesicle structures, resulting in variations in size and lamellarity. Small changes in the orientation of hydroxyl groups, as dictated by different carbohydrates, induced substantial differences in vesicle morphology. The use of PLD catalyzed enzymatic transphosphatidylation represents a powerful strategy for synthesis of novel glycophospholipid materials, which are otherwise difficult to achieve through traditional synthetic methods. By harnessing the complex nature and structurally rich diversity of carbohydrates, this approach enables the synthesis of an extensive variety of glycophospholipid conjugates with distinct properties. This work demonstrates an effective method for designing advanced lipid-based materials tailored for diverse applications such as drug delivery, nanotechnology, and biomedicine, where precise control of self-assembly and functionality is essential.<br/>}},
author = {{Barchan, Nikolina}},
isbn = {{978-91-8096-108-0}},
keywords = {{phospholipid; carbohydrate; transphosphatidylation; phospholipase D; lipid self-assembly; polar lipid}},
language = {{eng}},
publisher = {{Department of Biotechnology, Lund University}},
school = {{Lund University}},
title = {{Novel glycophospholipids: : Phospholipase D catalysed synthesis and characterization}},
url = {{https://lup.lub.lu.se/search/files/218605679/Avhandling_Nikolina_Barchan_LUCRIS.pdf}},
year = {{2025}},
}