Sugar Coated Formulations

The clustering of glycan ligands on the plasma membrane plays a crucial role in cell molecular recognition, as it enhances the selectivity and affinity of these ligands to specific receptors. Membrane lipids and proteins are distributed heterogeneously on the cell membrane, forming biophysically and...

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Main Author: Takan, Gokhan
Format: Thesis (University of Nottingham only)
Language:English
Published: 2024
Subjects:
Online Access:https://eprints.nottingham.ac.uk/78271/
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author Takan, Gokhan
author_facet Takan, Gokhan
author_sort Takan, Gokhan
building Nottingham Research Data Repository
collection Online Access
description The clustering of glycan ligands on the plasma membrane plays a crucial role in cell molecular recognition, as it enhances the selectivity and affinity of these ligands to specific receptors. Membrane lipids and proteins are distributed heterogeneously on the cell membrane, forming biophysically and biochemically distinct functional microdomains, such as lipid rafts. However, the spatial distribution of cell ligands and receptors within rafts and its effect on ligand binding and cellular recognition are not yet fully understood. This study has two primary objectives. Firstly, we aim to design ligands that can selectively sequester within liquid order and/or disordered phases within membranes. Secondly, we seek to investigate the effect of this phase sequestration on receptor binding. To achieve these goals, we have synthesized a library of mannose-MEAM polymers and galactose-containing control polymers with variable chain lengths via reversible-addition-fragment chain transfer (RAFT) polymerisation. We have then conjugated them to bis-azide containing cyanine membrane inserting dye by copper-catalysed azide-alkyne cycloaddition (CuAAC) click coupling. To analyse the phase partitioning behaviour of the resulting ligands, we have conducted experiments on synthetic Giant Unilamellar Vesicles (GUVs) and cell-derived Giant Plasma Membrane Vesicles (GPMVs). Receptor recognition potential of the ligands was also investigated on mannose receptor positive CHO cells. Through this study, we hope to gain a better understanding of how the spatial distribution of cell ligands and receptors within rafts affects ligand binding and cellular recognition.
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spelling nottingham-782712024-08-13T14:46:53Z https://eprints.nottingham.ac.uk/78271/ Sugar Coated Formulations Takan, Gokhan The clustering of glycan ligands on the plasma membrane plays a crucial role in cell molecular recognition, as it enhances the selectivity and affinity of these ligands to specific receptors. Membrane lipids and proteins are distributed heterogeneously on the cell membrane, forming biophysically and biochemically distinct functional microdomains, such as lipid rafts. However, the spatial distribution of cell ligands and receptors within rafts and its effect on ligand binding and cellular recognition are not yet fully understood. This study has two primary objectives. Firstly, we aim to design ligands that can selectively sequester within liquid order and/or disordered phases within membranes. Secondly, we seek to investigate the effect of this phase sequestration on receptor binding. To achieve these goals, we have synthesized a library of mannose-MEAM polymers and galactose-containing control polymers with variable chain lengths via reversible-addition-fragment chain transfer (RAFT) polymerisation. We have then conjugated them to bis-azide containing cyanine membrane inserting dye by copper-catalysed azide-alkyne cycloaddition (CuAAC) click coupling. To analyse the phase partitioning behaviour of the resulting ligands, we have conducted experiments on synthetic Giant Unilamellar Vesicles (GUVs) and cell-derived Giant Plasma Membrane Vesicles (GPMVs). Receptor recognition potential of the ligands was also investigated on mannose receptor positive CHO cells. Through this study, we hope to gain a better understanding of how the spatial distribution of cell ligands and receptors within rafts affects ligand binding and cellular recognition. 2024-07-24 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/78271/1/240524.Corrected_GT.pdf Takan, Gokhan (2024) Sugar Coated Formulations. PhD thesis, University of Nottingham. ligands cell membranes glycopolymers
spellingShingle ligands
cell membranes
glycopolymers
Takan, Gokhan
Sugar Coated Formulations
title Sugar Coated Formulations
title_full Sugar Coated Formulations
title_fullStr Sugar Coated Formulations
title_full_unstemmed Sugar Coated Formulations
title_short Sugar Coated Formulations
title_sort sugar coated formulations
topic ligands
cell membranes
glycopolymers
url https://eprints.nottingham.ac.uk/78271/