Inverting glucuronidation of hymecromone <i>in situ</i> by catalytic nanocompartments

Korpidou, Maria; Maffeis, Viviana; Dinu, Ionel Adrian; Schoenenberger, Cora‐Ann; Meier, Wolfgang; Palivan, Cornelia G.

doi:10.1039/d2tb00243d

Cited by 11 publications

(19 citation statements)

References 69 publications

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“…[ 28 ] Copolymers with PDMS as hydrophobic block and PMOXA as hydrophilic block are well suited for producing catalytic compartments because the polymer membrane is generally impermeable to small molecules but sufficiently flexible to enable the insertion of membrane proteins [ 29 ] and pore forming peptides such as melittin that enable communication with the compartment interior. [ 30 ] Accordingly, in situ catalysis has been achieved by luciferase [ 31 ] or glucuronidase [ 32 ] confined in the hydrophilic cavity of melittin‐permeabilized PMOXA 10 ‐ b ‐PDMS 25 based polymersomes. Melittin has been shown to induce pore formation in membranes formed by triblock PMOXA‐PDMS‐PMOXA and diblock PMOXA‐PDMS without destabilizing the vesicles.…”

Section: Resultsmentioning

confidence: 99%

“…[ 29 ] Melittin pore formation is dynamic and the pore size reported for lipid membranes vary from 0.4 [ 33 ] to 1.7 nm. [ 34 ] A number of substrates including glucose, AmplexRed [ 29 ] and 4‐methylumbelliferyl glucuronide [ 32 ] and the respective products have been shown to diffuse via melittin pores in and out of polymersomes.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…[21,22] In order to exclude differences related to the number of melittin pores, both types of CNCs were permeabilized with 25 µm melittin (final concentration), which results in ≈100 pores per CNC. [32,33,28] Furthermore, we surface-functionalized CNCs with 22-mer oligonucleotides in order to ultimately anchor them to a glass surface. For this purpose, CNCs were incubated with the 22-mer bearing a cholesterol moiety at the 3' end, which inserts into the hydrophobic region of the CNC membrane (Tables S3 and S4, Supporting Information).…”

Section: Dna Polymerase and Atp Sulfurylase Cncsmentioning

confidence: 99%

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A DNA‐Micropatterned Surface for Propagating Biomolecular Signals by Positional on‐off Assembly of Catalytic Nanocompartments

Maffeis

Hürlimann

Krywko‐Cendrowska

et al. 2022

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Signal transduction is pivotal for the transfer of information between and within living cells. The composition and spatial organization of specified compartments are key to propagating soluble signals. Here, a high‐throughput platform mimicking multistep signal transduction which is based on a geometrically defined array of immobilized catalytic nanocompartments (CNCs) that consist of distinct polymeric nanoassemblies encapsulating enzymes and DNA or enzymes alone is presented. The dual role of single entities or tandem CNCs in providing confined but communicating spaces for complex metabolic reactions and in protecting encapsulated compounds from denaturation is explored. To support a controlled spatial organization of CNCs, CNCs are patterned by means of DNA hybridization to a microprinted glass surface. Specifically, CNC‐functionalized DNA microarrays are produced where individual reaction compartments are kept in close proximity by a distinct geometrical arrangement to promote effective communication. Besides a remarkable versatility and robustness, the most prominent feature of this platform is the reversibility of DNA‐mediated CNC‐anchoring which renders it reusable. Micropatterns of polymer‐based nanocompartment assemblies offer an ideal scaffold for the development of the next generation responsive and communicative soft‐matter analytical devices for applications in catalysis and medicine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Dna Polymerase and Atp Sulfurylase Cncsmentioning

confidence: 99%

See 2 more Smart Citations

A DNA‐Micropatterned Surface for Propagating Biomolecular Signals by Positional on‐off Assembly of Catalytic Nanocompartments

Maffeis

Hürlimann

Krywko‐Cendrowska

et al. 2022

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“…However, it should be noted that OmpF allowed for the diffusion of molecules only up to 600 Da, limiting the possible applications of permeabilized polymersomes [ 90 ]. Apart from OmpF, melittin biopores can also be used for membrane permeabilization [ 161 ]. Melittin-permeabilized polymersomes made from PMOXA- b -PDMS encapsulating β-glucuronidase were prepared to invert the glucuronidation of drugs in situ.…”

Section: Applications Of Compartments In the Biomedical Fieldmentioning

confidence: 99%

Current Perspectives on Synthetic Compartments for Biomedical Applications

Heuberger

Korpidou

Eggenberger

et al. 2022

IJMS

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Nano- and micrometer-sized compartments composed of synthetic polymers are designed to mimic spatial and temporal divisions found in nature. Self-assembly of polymers into compartments such as polymersomes, giant unilamellar vesicles (GUVs), layer-by-layer (LbL) capsules, capsosomes, or polyion complex vesicles (PICsomes) allows for the separation of defined environments from the exterior. These compartments can be further engineered through the incorporation of (bio)molecules within the lumen or into the membrane, while the membrane can be decorated with functional moieties to produce catalytic compartments with defined structures and functions. Nanometer-sized compartments are used for imaging, theranostic, and therapeutic applications as a more mechanically stable alternative to liposomes, and through the encapsulation of catalytic molecules, i.e., enzymes, catalytic compartments can localize and act in vivo. On the micrometer scale, such biohybrid systems are used to encapsulate model proteins and form multicompartmentalized structures through the combination of multiple compartments, reaching closer to the creation of artificial organelles and cells. Significant progress in therapeutic applications and modeling strategies has been achieved through both the creation of polymers with tailored properties and functionalizations and novel techniques for their assembly.

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Synthetic Cells Revisited: Artificial Cells Construction Using Polymeric Building Blocks

Maffeis,

Heuberger,

Nikoletić

et al. 2023

Advanced Science

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The exponential growth of research on artificial cells and organelles underscores their potential as tools to advance the understanding of fundamental biological processes. The bottom–up construction from a variety of building blocks at the micro‐ and nanoscale, in combination with biomolecules is key to developing artificial cells. In this review, artificial cells are focused upon based on compartments where polymers are the main constituent of the assembly. Polymers are of particular interest due to their incredible chemical variety and the advantage of tuning the properties and functionality of their assemblies. First, the architectures of micro‐ and nanoscale polymer assemblies are introduced and then their usage as building blocks is elaborated upon. Different membrane‐bound and membrane‐less compartments and supramolecular structures and how they combine into advanced synthetic cells are presented. Then, the functional aspects are explored, addressing how artificial organelles in giant compartments mimic cellular processes. Finally, how artificial cells communicate with their surrounding and each other such as to adapt to an ever‐changing environment and achieve collective behavior as a steppingstone toward artificial tissues, is taken a look at. Engineering artificial cells with highly controllable and programmable features open new avenues for the development of sophisticated multifunctional systems.

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Inverting glucuronidation of hymecromone in situ by catalytic nanocompartments

Abstract: Glucuronidation is a metabolic pathway that inactivates many drugs including hymecromone. Adverse effects of glucuronide metabolites include a reduction of half-life circulation times and rapid elimination from the body. Herein,...

Cited by 11 publications

References 69 publications

A DNA‐Micropatterned Surface for Propagating Biomolecular Signals by Positional on‐off Assembly of Catalytic Nanocompartments

A DNA‐Micropatterned Surface for Propagating Biomolecular Signals by Positional on‐off Assembly of Catalytic Nanocompartments

Current Perspectives on Synthetic Compartments for Biomedical Applications

Synthetic Cells Revisited: Artificial Cells Construction Using Polymeric Building Blocks

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