| 1. |
- Cuapio, Angelica, et al.
(författare)
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NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals
- 2022
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Ingår i: Molecular Medicine. - : BioMed Central (BMC). - 1076-1551 .- 1528-3658. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021–000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1.
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| 2. |
- Gajdoš, Matúš, et al.
(författare)
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Chiral Alcohols from Alkenes and Water: Directed Evolution of a Styrene Hydratase
- 2023
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Ingår i: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 62:7
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Tidskriftsartikel (refereegranskat)abstract
- Enantioselective synthesis of chiral alcohols through asymmetric addition of water across an unactivated alkene is a highly sought-after transformation and a big challenge in catalysis. Herein we report the identification and directed evolution of a fatty acid hydratase from Marinitoga hydrogenitolerans for the highly enantioselective hydration of styrenes to yield chiral 1-arylethanols. While directed evolution for styrene hydration was performed in the presence of heptanoic acid to mimic fatty acid binding, the engineered enzyme displayed remarkable asymmetric styrene hydration activity in the absence of the small molecule activator. The evolved styrene hydratase provided access to chiral alcohols from simple alkenes and water with high enantioselectivity (>99 : 1 e.r.) and could be applied on a preparative scale.
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| 3. |
- Hammer, Stephan C., et al.
(författare)
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Squalene hopene cyclases : highly promiscuous and evolvable catalysts for stereoselective CC and CX bond formation
- 2013
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Ingår i: Current opinion in chemical biology. - : Elsevier. - 1367-5931 .- 1879-0402. ; 17:2, s. 293-300
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Tidskriftsartikel (refereegranskat)abstract
- A review. We review here how the inherent promiscuous nature, as well as the evolvability of terpene cyclase enzymes enables new applications in chem. We mainly focus on squalene hopene cyclases, class II triterpene synthases that use a proton-initiated cationic polycyclization cascade to form carbopolycyclic products. We highlight recent findings to demonstrate that these enzymes are capable of activating different functionalities other than the traditional terminal isoprene CC-group as well as being compatible with a wide range of nucleophiles beyond the 'ene-functionality'. Thus, squalene hopene cyclases demonstrate a great potential to be used as a toolbox for general Bronsted acid catalysis.
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| 4. |
- Hammer, Stephan C., et al.
(författare)
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Stereoselective Friedel-Crafts alkylation catalyzed by squalene hopene cyclases
- 2012
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Ingår i: Tetrahedron. - : Elsevier Ltd.. - 0040-4020 .- 1464-5416. ; 68:Copyright (C) 2013 American Chemical Society (ACS). All Rights Reserved., s. 7624-7629
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Tidskriftsartikel (refereegranskat)abstract
- In org. synthesis the Friedel-Crafts alkylation is of eminent importance, as it is a key reaction in many synthetic routes. A general access to enzymic Friedel-Crafts alkylations would be very beneficial due to the high selectivity of biocatalysts. We used designed polyprenyl Ph ethers to specifically address this reaction by using squalene hopene cyclases as catalysts. Polycyclic products with arom. rings constituting important biol. active compds. were obtained. Our results demonstrate that squalene hopene cyclases can be utilized for Friedel-Crafts alkylations and reveal the potential of these enzymes for chiral Bronsted acid catalysis.
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| 5. |
- Nebel, Bernd A., et al.
(författare)
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A Career in Catalysis : Bernhard Hauer
- 2023
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Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 13:13, s. 8861-8889
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Forskningsöversikt (refereegranskat)abstract
- On the occasion of Professor Bernhard Hauer′s (partial) retirement, we reflect on and highlight his distinguished career in biocatalysis. Bernhard, a biologist by training, has greatly influenced biocatalysis with his vision and ideas throughout his four-decade career. The development of his career went hand in hand with the evolution of biocatalysis and the application and development of enzymes for chemical processes. In this Account, we present selected examples of his early work on the development of enzymes and their application in an industrial setting, with a focus on his specific contributions to harnessing the catalytic power of enzymes for novel reactions and the understanding and engineering of flexible loops and channels on catalysis.
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| 6. |
- Syrén, Per-Olof, et al.
(författare)
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Entropy is Key to the Formation of Pentacyclic Terpenoids by Enzyme-Catalyzed Polycyclization
- 2014
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 53:19, s. 4845-4849
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Tidskriftsartikel (refereegranskat)abstract
- Polycyclizations constitute a cornerstone of chemistry and biology. Multicyclic scaffolds are generated by terpene cyclase enzymes in nature through a carbocationic polycyclization cascade of a prefolded polyisoprene backbone, for which electrostatic stabilization of transient carbocationic species is believed to drive catalysis. Computational studies and site-directed mutagenesis were used to assess the contribution of entropy to the polycyclization cascade catalyzed by the triterpene cyclase from A. acidocaldarius. Our results show that entropy contributes significantly to the rate enhancement through the release of water molecules through specific channels. A single rational point mutation that results in the disruption of one of these water channels decreased the entropic contribution to catalysis by 60kcalmol(-1). This work demonstrates that entropy is the key to enzyme-catalyzed polycyclizations, which are highly relevant in biology since 90% of all natural products contain a cyclic subunit.
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