Imidazole Headgroup Phospholipid Shows Asymmetric Distribution in Vesicles and Zinc-Dependent Esterase Activity

Artificial lipids have become increasingly important in generating novel nanoenzymes and nanoparticles. Imidazole has been well established as a versatile catalyst in synthetic chemistry and through its related amino acid histidine in enzymes. By exploiting the transphosphatidylation reaction of pho...

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Main Authors: Gabriela Sachet-Fernandez, James W. Hindley, Oscar Ces, Rüdiger Woscholski
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/14/11/1363
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author Gabriela Sachet-Fernandez
James W. Hindley
Oscar Ces
Rüdiger Woscholski
author_facet Gabriela Sachet-Fernandez
James W. Hindley
Oscar Ces
Rüdiger Woscholski
author_sort Gabriela Sachet-Fernandez
collection DOAJ
description Artificial lipids have become increasingly important in generating novel nanoenzymes and nanoparticles. Imidazole has been well established as a versatile catalyst in synthetic chemistry and through its related amino acid histidine in enzymes. By exploiting the transphosphatidylation reaction of phospholipase D, the choline headgroup of phosphatidyl choline was exchanged for the imidazole moiety containing histidinol. Here, we introduce a novel phosphatidylhistidinol (PtdHisOH) lipid and characterise it with respect to its catalytic abilities and its ability to modulate vesicle size. Our data reveal a zinc-dependent esterase activity that was strongest in vesicles and micelles, with slower catalytic rates being observed in flat lipid presentation systems and two-phase systems, indicating the importance of surface presentation and curvature effects on the catalytic activity of PtdHisOH. Such lipids offer the opportunity to impart de novo catalytic functionality to self-assembled lipid systems such as synthetic cells, leading to the development of new technologies for biocatalysis applications.
format Article
id doaj-art-7d4028168ac24733bd0aea63fc363f2b
institution OA Journals
issn 2218-273X
language English
publishDate 2024-10-01
publisher MDPI AG
record_format Article
series Biomolecules
spelling doaj-art-7d4028168ac24733bd0aea63fc363f2b2025-08-20T02:08:12ZengMDPI AGBiomolecules2218-273X2024-10-011411136310.3390/biom14111363Imidazole Headgroup Phospholipid Shows Asymmetric Distribution in Vesicles and Zinc-Dependent Esterase ActivityGabriela Sachet-Fernandez0James W. Hindley1Oscar Ces2Rüdiger Woscholski3Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London W12 0BZ, UKDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, London W12 0BZ, UKDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, London W12 0BZ, UKDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, London W12 0BZ, UKArtificial lipids have become increasingly important in generating novel nanoenzymes and nanoparticles. Imidazole has been well established as a versatile catalyst in synthetic chemistry and through its related amino acid histidine in enzymes. By exploiting the transphosphatidylation reaction of phospholipase D, the choline headgroup of phosphatidyl choline was exchanged for the imidazole moiety containing histidinol. Here, we introduce a novel phosphatidylhistidinol (PtdHisOH) lipid and characterise it with respect to its catalytic abilities and its ability to modulate vesicle size. Our data reveal a zinc-dependent esterase activity that was strongest in vesicles and micelles, with slower catalytic rates being observed in flat lipid presentation systems and two-phase systems, indicating the importance of surface presentation and curvature effects on the catalytic activity of PtdHisOH. Such lipids offer the opportunity to impart de novo catalytic functionality to self-assembled lipid systems such as synthetic cells, leading to the development of new technologies for biocatalysis applications.https://www.mdpi.com/2218-273X/14/11/1363phospholipase Denzyme-assisted synthesisallosterictemperaturealcohollipid
spellingShingle Gabriela Sachet-Fernandez
James W. Hindley
Oscar Ces
Rüdiger Woscholski
Imidazole Headgroup Phospholipid Shows Asymmetric Distribution in Vesicles and Zinc-Dependent Esterase Activity
Biomolecules
phospholipase D
enzyme-assisted synthesis
allosteric
temperature
alcohol
lipid
title Imidazole Headgroup Phospholipid Shows Asymmetric Distribution in Vesicles and Zinc-Dependent Esterase Activity
title_full Imidazole Headgroup Phospholipid Shows Asymmetric Distribution in Vesicles and Zinc-Dependent Esterase Activity
title_fullStr Imidazole Headgroup Phospholipid Shows Asymmetric Distribution in Vesicles and Zinc-Dependent Esterase Activity
title_full_unstemmed Imidazole Headgroup Phospholipid Shows Asymmetric Distribution in Vesicles and Zinc-Dependent Esterase Activity
title_short Imidazole Headgroup Phospholipid Shows Asymmetric Distribution in Vesicles and Zinc-Dependent Esterase Activity
title_sort imidazole headgroup phospholipid shows asymmetric distribution in vesicles and zinc dependent esterase activity
topic phospholipase D
enzyme-assisted synthesis
allosteric
temperature
alcohol
lipid
url https://www.mdpi.com/2218-273X/14/11/1363
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AT oscarces imidazoleheadgroupphospholipidshowsasymmetricdistributioninvesiclesandzincdependentesteraseactivity
AT rudigerwoscholski imidazoleheadgroupphospholipidshowsasymmetricdistributioninvesiclesandzincdependentesteraseactivity