DNA-Programmed Chemical Synthesis in Nano-sized Lipid Compartments

Xinwei Tian

doi:10.21996/266q-8e58

DNA-Programmed Chemical Synthesis in Nano-sized Lipid Compartments

Xinwei Tian

Publikation: Afhandling › Ph.d.-afhandling

98 Downloads (Pure)

Abstract

Lipid nanoreaktorer er selvmonterede, biokompatible reaktionsbeholdere, der kan være vært for vandige eller membran-associerede (bio)kemiske reaktioner. Nanoreaktorer giver ultra-miniaturisering ned til zeptolitervolumener pr. kar, men rumlig-temporal kontrol over dem - på individ- eller befolkningsniveau - er fortsat udfordrende. De lipid-nukleinsyrekonjugater (LiNAs) medierede liposomfusion udviklet i Assoc. Prof. S. Vogel-gruppen tillader blanding af de vandige opløsninger indesluttet i deres indre.

I denne ph.d.-afhandling rapporterer vi for første gang om DNA-programmerede lipid-nanoreaktorer (DPLNs), der udfører kemiske reaktioner og syntetiserer forskellige kulhydratmimetika som modelforbindelser. Det kemiske omdannelsesudbytte var ret pænt, tilskrevet den meget effektive indholdsblanding og lav lækagefri fusion. Optimering af lipidsammensætningen øger i høj grad fusionsydelsen. Problematisk passiv lækage i diffusionen af reaktanter under kemiske transformationer er blevet effektivt undertrykt via PEGyleret DOPE-modifikation på vesikeloverfladen. Gennem selektiv sammensmeltning af forskellige populationer af nanoreaktorer, der indkapsler mono- og oligosaccharidazider og alkynylfarvestoffer. Vi opnåede således kvantitative data for ti forskellige triazol-bundne kulhydrat-Cy5-konjugater dannet af stammefremmende azidalkyn-cycloadditioner og demonstrerede en to-trins reaktion udløst af kaskadisk nanoreaktorfusion. Undersøgelsen giver en detaljeret, trin-for-trin liste over eksperimenter, der kan bruges til at lave DNAprogrammerede liposomfusions-nanoreaktorer og åbner op for nye muligheder inden for kemi, biologi og andre områder.

Originalsprog	Engelsk
Bevilgende institution	Syddansk Universitet
Vejledere/rådgivere	Vogel, Stefan, Hovedvejleder
Dato for forsvar	30. okt. 2023
Udgiver	Syddansk Universitet. Det Naturvidenskabelige Fakultet
DOI	https://doi.org/10.21996/266q-8e58
Status	Udgivet - 4. nov. 2023

Note vedr. afhandling

Den fulde afhandling kan læses på SDUs bibliotek.

Dokumenter og links

10.21996/266q-8e58

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1 Tidsskriftartikel

DNA-Programmed Lipid Nanoreactors for Synthesis of Carbohydrate Mimetics by Fusion of Aqueous Sub-attoliter Compartments
Tian, X., Risgaard, N. A., Löffler, P. M. G. & Vogel, S., 24. aug. 2023, I: Journal of the American Chemical Society. 145, 36, s. 19633–19641
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Citationsformater

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abstract = "Lipid nanoreactors are self-assembled, biocompatible reaction vessels that can host aqueous or membrane-associated (bio)chemical reactions. Nanoreactors provide ultra-miniaturization down to zeptoliter volumes per vessel, but spatio-temporal control over them - at the individual or population level - remains challenging. The lipid-nucleic acid conjugates (LiNAs) mediated liposome fusion developed in the Assoc. Prof. S. Vogel group allows the mixing of the aqueous solutions entrapped within their interior. In this PhD thesis, we for the first time, report DNA-programmed lipid nanoreactors (D-PLNs) that operate chemical reactions, synthesizing different carbohydrate mimetics as model compounds. The chemical conversion yield was pretty nicely, attributed to the highly efficient content mixing and low leakagefree fusion. Optimizing the lipid composition largely increases the fusion performance. Problematic passive leakage in the diffusion of reactants during chemical transformations has been effectively suppressed via PEGylated DOPE modification on the vesicle surface. Through selectively fusing distinct populations of nanoreactors encapsulating mono- and oligosaccharide azides and alkynyl-dyes. We thus obtained quantitative data for ten different triazole-linked carbohydrate-Cy5 conjugates formed by strain-promoted azide-alkyne cycloadditions and demonstrated a two-step reaction triggered by cascadic nanoreactor fusion. The study gives a detailed, step-by-step list of experiments that can be used to make DNA-programmed liposome fusion nanoreactors and opens up new possibilities in chemistry, biology, and other fields. ",

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AB - Lipid nanoreactors are self-assembled, biocompatible reaction vessels that can host aqueous or membrane-associated (bio)chemical reactions. Nanoreactors provide ultra-miniaturization down to zeptoliter volumes per vessel, but spatio-temporal control over them - at the individual or population level - remains challenging. The lipid-nucleic acid conjugates (LiNAs) mediated liposome fusion developed in the Assoc. Prof. S. Vogel group allows the mixing of the aqueous solutions entrapped within their interior. In this PhD thesis, we for the first time, report DNA-programmed lipid nanoreactors (D-PLNs) that operate chemical reactions, synthesizing different carbohydrate mimetics as model compounds. The chemical conversion yield was pretty nicely, attributed to the highly efficient content mixing and low leakagefree fusion. Optimizing the lipid composition largely increases the fusion performance. Problematic passive leakage in the diffusion of reactants during chemical transformations has been effectively suppressed via PEGylated DOPE modification on the vesicle surface. Through selectively fusing distinct populations of nanoreactors encapsulating mono- and oligosaccharide azides and alkynyl-dyes. We thus obtained quantitative data for ten different triazole-linked carbohydrate-Cy5 conjugates formed by strain-promoted azide-alkyne cycloadditions and demonstrated a two-step reaction triggered by cascadic nanoreactor fusion. The study gives a detailed, step-by-step list of experiments that can be used to make DNA-programmed liposome fusion nanoreactors and opens up new possibilities in chemistry, biology, and other fields.

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DO - 10.21996/266q-8e58

M3 - Ph.D. thesis

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ER -

DNA-Programmed Chemical Synthesis in Nano-sized Lipid Compartments

Abstract

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DNA-Programmed Lipid Nanoreactors for Synthesis of Carbohydrate Mimetics by Fusion of Aqueous Sub-attoliter Compartments

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