| 1. |
- Slagbrand, Tove, et al.
(författare)
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Bimetallic Catalysis : Asymmetric Transfer Hydrogenation of Sterically Hindered Ketones Catalyzed by Ruthenium and Potassium
- 2015
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Ingår i: ChemCatChem. - : WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. - 1867-3880 .- 1867-3899. ; 7:21, s. 3445-3449
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Tidskriftsartikel (refereegranskat)abstract
- An efficient protocol for the asymmetric reduction of sterically hindered ketones under transfer-hydrogenation conditions was developed. The corresponding chiral alcohols were obtained in good to excellent yields with enantiomeric excess values up to 99%. The role of the cation associated with the base present in the reduction reaction was investigated. In contrast to previous studies on this catalyst system, potassium ions rather than lithium ions significantly enhanced the reaction outcome.
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| 2. |
- Cerrato, Carmine Pasquale, et al.
(författare)
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Intracellular delivery of therapeutic antisense oligonucleotides targeting mRNA coding mitochondrial proteins by cell-penetrating peptides
- 2020
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Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 8:47, s. 10825-10836
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Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides are a promising therapeutic strategy for a wide variety of degenerative diseases, ageing, and cancer. Among the multitude of cell-penetrating peptides, PepFect14 has been preferentially used in our laboratory for oligonucleotide delivery into cells and in vivo mouse models. However, this activity has mainly been reported towards cytoplasm and nuclei, while the mentioned disorders have been linked to mitochondrial defects. Here, we report a library generated from a combinatorial covalent fusion of a mitochondrial-penetrating peptide, mtCPP1, and PepFect14 in order to deliver therapeutic biomolecules to influence mitochondrial protein expression. The non-covalent complexation of these peptides with oligonucleotides resulted in nano-complexes affecting biological functions in the cytoplasm and on mitochondria. This delivery system proved to efficiently target mitochondrial genes, providing a framework for the development of mitochondrial peptide-based oligonucleotide technologies with the potential to be used as a treatment for patients with mitochondrial disorders.
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| 3. |
- Cerrato, Carmine Pasquale, et al.
(författare)
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Intracellular Delivery of Therapeutic Antisense Oligonucleotides Targeting mRNACoding Mitochondrial Proteins by Cell-Penetrating Peptides
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Cell-penetrating peptides are a promising therapeutic strategy for a wide variety of degenerative diseases, ageing, and cancer. Among the multitude of cellpenetrating peptides, PepFect14 has been preferentially used in our laboratory for oligonucleotide delivery into cells and in vivo mouse models. However, this activity has mainly been reported towards cytoplasm and nuclei, while the mentioned disorders have been linked to mitochondrial defects. Here, we report a library generated from a combinatorial covalent fusion of a mitochondrial-penetrating peptide, mtCPP1, and PepFect14 in order to deliver therapeutic biomolecules to influence mitochondrial protein expression. The non-covalent complexation of these peptides with oligonucleotides resulted in nanocomplexes affecting biological functions in the cytoplasm and on mitochondria. This delivery system proved to efficiently target mitochondrial genes, providing a framework for the development of mitochondrial peptide-based oligonucleotide technologies with the potential to be used as a treatment for patients with mitochondrial disorders.
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| 4. |
- Cerrato, C. P., et al.
(författare)
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Mitochondrial Targeting Probes, Drug Conjugates, and Gene Therapeutics
- 2022
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Ingår i: Cell Penetrating Peptides. - New York, NY : Springer Nature. ; 2383, s. 429-446
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Bokkapitel (refereegranskat)abstract
- Mitochondria represent an important drug target for many phatology, including neurodegeneration, metabolic disease, heart failure, ischemia-reperfusion injury, and cancer. Mitochondrial dysfunctions are caused by mutation in mitochondrial DNA or in nuclear genes encoding mitochondrial proteins. Cell-penetrating peptides (CPPs) have been employed to overcome biological barriers, target this organelle, and therapeuticaly restore mitochondrial functions. Here, we describe recent methods used to deliver oligonucleotides targeting mitochondrial protein by using mitochondrial penetrating peptides. In particular, we highlight recent advances of formulated peptides/oligonucleotides nanocomplexes as a proof-of-principle for pharmaceutical form of peptide-based therapeutics.
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| 5. |
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| 6. |
- Delplace, Vianney, et al.
(författare)
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Inverse Electron-Demand Diels-Alder Methylcellulose Hydrogels Enable the Co-delivery of Chondroitinase ABC and Neural Progenitor Cells
- 2020
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 21:6, s. 2421-2431
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Tidskriftsartikel (refereegranskat)abstract
- A hydrogel that can deliver both proteins and cells enables the local microenvironment of transplanted cells to be manipulated with a single injection. Toward this goal, we designed a hydrogel suitable for the co-delivery of neural stem cells and chondroitinase ABC (ChABC), a potent enzyme that degrades the glial scar that forms after central nervous system (CNS) injury. We leveraged the inverse electron-demand Diels-Alder reaction between norbomene and methylphenyltetrazine to form rapidly gelling (<15 min) crosslinked methylcellulose (MC) hydrogels at physiological temperature and pH, with Young's modulus similar to that of brain tissue (1-3 kpa), and degradable, disulfide-containing crosslinkers. To achieve tunable, affinity-controlled release of a ChABC-Src homology 3 (SH3) fusion protein, we immobilized norbornene-functionalized SH3-binding peptides onto MC-methylphenyltetrazine and observed release of bioactive ChABC-SH3 over 4 days. We confirmed cytocompatibility by evaluating neural progenitor cell survival and proliferation. The combined encapsulation of neural stem cells and chondroitinase ABC from one hydrogel lays the framework for future in vivo studies to treat CNS injuries.
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| 7. |
- Fuoco, Tiziana, PhD, 1986-, et al.
(författare)
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Organocatalytic strategy to telechelic oligo(ε-caprolactone-co-p-dioxanone): Photocurable macromonomers for polyester networks
- 2020
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Ingår i: European Polymer Journal. - : Elsevier BV. - 0014-3057 .- 1873-1945. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- We have designed photocurable, telechelic macromonomers consisting of random oligo(ε-caprolactone-co-p-dioxanone), oligo(CL-co-DX), and demonstrated their suitability for preparing pliable polyester networks whose properties resemble those of gels.A versatile and effective metal-free co-oligomerization, catalyzed by diphenyl phosphate, was developed in bulk and at room temperature. A high rate of conversion of monomers was achieved and oligo(CL-co-DX)s with different composition and topology were obtained with controlled molar mass, approx. 2000 g mol−1, low dispersity and a random distribution of the two monomeric units. Kinetics analysis of the reaction disclosed a faster incorporation rate for the p-dioxanone (DX) than ε-caprolactone (CL). The extrapolated rate constant, kDX, was 0.030 min−1 against a kCL of 0.013 min−1. The reactivity ratios were respectively 2.7 (rDX) and 0.28 (rCL). A detailed NMR analysis was performed to elucidate the structure of the co-oligomers, which could be precisely controlled by varying the monomer feed ratio and initiator. Depending on the composition, amorphous to semicrystalline oligomers with melting points close to room temperature were obtained, which after acrylation of the chain-end gave polyester networks with high swelling capacity up to 700%, and water uptake up to 70%.
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| 8. |
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| 9. |
- Kivijärvi, Tove
(författare)
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Exploiting chemical control in biomaterials
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chemistry and biology at the interphase will most likely give many of the answers to tomorrows medical challenges. Creating solutions to the problems at this interphase is benefiting from a collaborative research approach, driven by the need for development of chemistries or devices solving medical problems. However, several important challenges remain to fulfil a successful symphony. The most crucial aspect is to understand the communication between these processes while having fundamental control over the underlying processes.The central theme of this thesis has been to develop functional degradable polymers and materials aimed to integrate with the cell microenvironment, and through control over the chemistry modulate the synthesis, material or biological processes. This was realized on several hierarchical levels. The primary initial focus on control over polymer microstructure was achieved by fundamental exploration on the kinetics and thermodynamics governing the reaction. The polymerization work was then transitioned into the controllable fabrication of a material bearing short-term tissue relevant properties with long-term degradability exploited by biorthogonal chemical control. Lastly, control over protein presentation was realized through two complimentary light-guided chemical reactions with an ultimate ability to control cellular fate.This thesis reflects an academic research journey culminating in an appreciation of the importance of exploiting chemical control to enable well-defined polymers and materials enabling modulation of the overarching systems that they are aimed to exist within. To truly solve important biological problems; chemists, material scientists and biologists alike must remain truly engaged and fundamental to their own expertise but also continuously bridge their communication by maintaining curiosity and understanding for one another. Only then, will innovative solutions to tomorrow’s societal problems be created.
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| 10. |
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