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High resolution 3D printed biocatalytic reactor core with optimized efficiency for continuous flow synthesis
No full textData associated with publication: S.J. Attwood, D. Leech, Y. He, A. Croft, R. J.M. Hague, D.J. Irvine, R.D. Wildman, A. Pordea, High resolution 3D printed biocatalytic reactor core with optimized efficiency for continuous flow synthesis, Chemical Engineering Science (2024)
Chemogenetic protein engineering: optimization of artificial metalloenzymes for oxidation and reduction reactions
Get PDFThèse de doctorat : Université de Neuchâtel, 2008 ; Th.2010La capacité d’optimiser ou de créer de nouveaux catalyseurs pour des transformations énantioselectives a un impact majeur dans les applications de la chimie actuelle. Les métalloenzymes artificielles se situent à l’interface entre la catalyse organométallique et celle enzymatique et ont un immense potentiel d’optimisation, qui combine des méthodes chimiques et génétiques pour créer la diversité. En termes d’activité, répertoire de réactions et de substrats ou conditions opératoires, elles exploitent la versatilité de la chimie organométallique. Par contre, l’énantiosélectivité est déterminée par la protéine, qui assure une seconde sphère de coordination très bien définie, réminiscente des biocatalyseurs. L’incorporation des complexes biotinylés catalytiquement actifs dans la streptavidine permet la création des métalloenzymes artificielles pour le transfert hydrogénant des cètones prochirales. Les tendances générales de l’activité et de la sélectivité des catalyseurs sont assurées par le choix de la partie organométallique suite à un premier criblage. L’étude de la structure d’une telle enzyme artificielle est à la base d’une « évolution rationnelle », dans laquelle des étapes successives de mutagenèse de saturation à des positions attentivement choisies sont combinées avec un criblage de l’énantiosélectivité. Cette méthode permet l’identification des catalyseurs hautement sélectifs pour la réduction de substrats difficiles, comme par exemple les dialkyl cètones. Le réseau des liaisons hydrogène dans le site actif de la streptavidine est très bien défini et permet également l’insertion de composés non-biotinylés, tels des ions métalliques catalytiquement actifs. L’environnement asymétrique assuré par la protéine peut être exploité dans des réactions de sulfoxydation énantiosélective catalysée par du vanadium. Ces réactions montrent que l’incorporation spécifique d’un métal peut transformer une protéine sans activité enzymatique en un biocatalyseur utilisé en synthèse organique., The ability to optimize or to find new catalysts for enantioselective transformations has a major impact in today’s chemistry. Artificial metalloenzymes lie at the interface between organometallic and enzymatic catalysis and have an immense optimization potential, which combines chemical and genetic methods to screen diversity space. In terms of activity, reaction repertoire, substrate range and operating conditions, they take advantage of the versatility of the organometallic chemistry. In contrast, the enantioselectivity is determined by the biomolecular scaffold, which provides a well defined second coordination sphere to the organometallic moiety, reminiscent of enzymes. Incorporation of catalytically active biotinylated complexes within streptavidin affords artificial metalloenzymes for the transfer hydrogenation of prochiral ketones. The activity and selectivity trends of the catalysts are ensured by the choice of the chemical fragment in a first screening round. Insight into the structure of an artificial enzyme forms the basis of a designed evolution step, which relies on successive rounds of saturation mutagenesis at carefully selected positions and screening for enantioselectivity. This procedure allows the identification of highly selective scaffolds for the reduction of challenging substrates, such as dialkyl ketones. The well-tailored hydrogen bond network of streptavidin’s binding cavity can also accommodate non-biotinylated frameworks, such as catalytically active metal ions. The enantiodiscriminating environment provided by the host protein can be exploited to perform highly enantioselective vanadium-catalyzed oxidations of several prochiral sulfides, demonstrating that specific metal binding can transform a non-enzymatic protein into an enantioselective biocatalyst with synthetic utility
Data for Encapsulation of copper phenanthroline within horse spleen apoferritin: characterisation, cytotoxic activity and ability to retain temozolomide
No full textIn this work, we investigate the encapsulation of a Cu(II)-phenanthroline complex (Cu(phen)(NO3)2) within HSAFt, as a potential vector for the delivery of anticancer agents. We immobilise Cu(II) within the protein as a metal complex with 1,10-phenanthroline, to form HSAFt-Cu(phen) dense particles that can be stored for months at low temperature (-20 °C). We subsequently characterise HSAFt-Cu(phen) by drug release studies and cytotoxicity assays against colorectal cancer cells and glioblastoma multiforme cells. We also investigate whether the presence of Cu(phen) inside HSAFt can offer additional benefits for the encapsulation and antitumour activity of anticancer drugs such as temozolomide (TMZ)
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Biocatalyst-artificial metalloenzyme cascade based on alcohol dehydrogenase
Get PDF© The Royal Society of Chemistry. Chemo-enzymatic cascades of enzymes with transition metal catalysts can offer efficient synthetic strategies, but their development is challenging due to the incompatibility between proteins and transition metal complexes. Rhodium catalysts can be combined with alcohol dehydrogenases to regenerate nicotinamide cofactors using formate as the hydride donor. However, their use is limited, due to binding of the metals to residues on the enzyme surface, leading to mutual enzyme and catalyst inactivation. In this work, we replaced the zinc from Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) with Rh(iii) catalysts possessing nitrogen donor ligands, by covalent conjugation to the active site cysteine, to create artificial metalloenzymes for NADP+ reduction. TbADH was used as protein scaffold for both alcohol synthesis and the recycling of the cofactor, by combination of the chemically modified species with the non-modified recombinant enzyme. Stability studies revealed that the incorporation of the catalysts into the TbADH pocket provided a shielding environment for the metal catalyst, resulting in increased stability of both the recycling catalyst and the ADH. The reduction of a representative ketone using this novel alcohol dehydrogenase-artificial formate dehydrogenase cascade yielded better conversions than in the presence of free metal catalyst
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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