Papers by Christian Trindler
Mein erster Dank gilt Prof. Dr. Thomas Carell für die interessante und vielseitige Themenstellung... more Mein erster Dank gilt Prof. Dr. Thomas Carell für die interessante und vielseitige Themenstellung. Seine Begeisterungsfähigheit und sein Optimismus haben entscheidend zum Erfolg der Arbeit beigetragen. Ich danke zudem für die exzellenten Arbeitsbedingungen, die angenehme Atmosphäre und für die wissenschaftliche Freiheit, die er mir gewährt hat. Herrn Prof. Dr. Hendrik Zipse danke ich für die Übernahme des Koreferats. Besonderen Dank geht an Herrn Prof. Dr. Konstatin Karaghiosoff für die Aufnahme der Röntgenstrukturanalysen. Während meiner Dissertation wurde ich vom Marie-Curie Forschungsnetzwerk der EU und von Novartis finanziell unterstützt, für was ich mich ebenfalls sehr bedanken möchte. Frau Gärtner danke ich für die Unterstützung und Hilfe bei organisatorischen Belangen. Grossen Dank auch an Sabine Voß (mit Scharf-S wohlgemerkt!) für die synthetische Unterstützung und speziell für die Hilfe bei etwaigen Beschwerdeanrufen, die sie immer sehr schlagkräftig gemeistert hat. Den Mitarbeitern der Analytikabteilung, Herrn Werner Spahl und Frau Sonja Kosak für die Anfertigung der Massenspektren, Frau Claudia Dubler und Dr. David Stevenson für jede Menge Spezialaufnahmen und Erläuterungen rund um die Welt des NMRs. Allen Mitarbeitern der Arbeitsgruppe danke ich für die angenehme Atmosphäre. Ich werde die Ausflüge und Unternehmungen vermissen. Als letzter Kämpfer des Schuftovich-Labors danke ich Philipp Gramlich und Christian Wirges für die witzige Zeit und Spass während der Arbeit. Mein ehemaliger Diplomand Julian Willibald und meine Ex-Laborkollegen Stephan Prill, Johannes Harder und Felix Gnerlich geben ihr Bestes, die gute Atmosphäre aufrecht zu erhalten. Besonders Julian verdanke ich viele gute Diskussionen, wenn es mal wieder um physikalische Aspekte rund um den Elektronentransfer ging. Für die musikalischen Effekte und Gesangs-und Tanzeinlagen haben Stephan und ich ein prima Team gebildet. Für synthetische Fragen war der Weg bis ins Biochemie-Labor zwar weit, aber meist rauschte Martin Münzel energiegeladen sowieso in und um den HPLC-Raum, so dass der Weg erspart blieb. In diesem Sinne danke ich auch Daniel Globisch für die massenanalytischen Debromierungsbestimmungen und seinem erfrischenden Optimismus, der sehr geholfen hat. Auch Tobias Brückl danke ich für viele gute synthetische Ideen und wünsche ihm viel Spass und Erfolg bei Phil Baran. Thomas Reissner danke ich für all die Kinobesuche der spezielleren Art und für die Unterstützung bei den Auf und Abs während der Dissertation. Gerade die sportlichen
Food Chemistry, 2022
Peas as an alternative protein source have attracted a great deal of interest from the food indus... more Peas as an alternative protein source have attracted a great deal of interest from the food industry and consumers in recent years. However, pea proteins usually do not taste neutral and exhibit a distinct flavor, often characterized as "beany". This is usually contrasted by the food industry's desire for sensory neutral protein sources. In this review, we highlight the current state of knowledge about the aroma of peas and its changes along the pea value chain. Possible causes and origins, and approaches to reduce or eliminate the aroma constituents are presented. Fermentative methods were identified as interesting to mitigate undesirable off-flavors. Major potential has also been discussed for breeding, as there appears to be a considerable leverage at this point in the value chain: a reduction of plant-derived flavors, precursors, or substrates involved in off-flavor evolution could prevent the need for expensive removal later.
Effects of Nanoconfinement on Catalysis, 2017
While chemists are developing confined environments for catalysis, nature has evolved highly elab... more While chemists are developing confined environments for catalysis, nature has evolved highly elaborate compartments to carry out reactions. Proteins offer such catalytic nano-environments that accept specific substrates to yield highly enantioenriched products. Metalloenzymes form a subclass that combines the functional diversity of proteins with the promiscuous activities of metals. In recent years, a variety of artificial metalloenzymes (ArMs) has been created upon incorporation of metal complexes into a protein scaffold. The following chapter discusses some of the protein scaffolds exploited for the creation of artificial metalloenzymes. Focus is laid on artificial metalloenzymes that catalyze abiotic and asymmetric reactions. Each subchapter presents the unique characteristics of a scaffold followed by a description of the reactions that were performed with it
Journal of the American Chemical Society, Jan 3, 2018
Artificial metalloenzymes (ArMs), which combine an abiotic metal cofactor with a protein scaffold... more Artificial metalloenzymes (ArMs), which combine an abiotic metal cofactor with a protein scaffold, catalyze various synthetically useful transformations. To complement the natural enzymes' repertoire, effective optimization protocols to improve ArM's performance are required. Here we report on our efforts to optimize the activity of an artificial transfer hydrogenase (ATHase) using Escherichia coli whole cells. For this purpose, we rely on a self-immolative quinolinium substrate which, upon reduction, releases fluorescent umbelliferone, thus allowing efficient screening. Introduction of a loop in the immediate proximity of the Ir-cofactor afforded an ArM with up to 5-fold increase in transfer hydrogenation activity compared to the wild-type ATHase using purified mutants.
Nature, Sep 29, 2016
The field of biocatalysis has advanced from harnessing natural enzymes to using directed evolutio... more The field of biocatalysis has advanced from harnessing natural enzymes to using directed evolution to obtain new biocatalysts with tailor-made functions. Several tools have recently been developed to expand the natural enzymatic repertoire with abiotic reactions. For example, artificial metalloenzymes, which combine the versatile reaction scope of transition metals with the beneficial catalytic features of enzymes, offer an attractive means to engineer new reactions. Three complementary strategies exist: repurposing natural metalloenzymes for abiotic transformations; in silico metalloenzyme (re-)design; and incorporation of abiotic cofactors into proteins. The third strategy offers the opportunity to design a wide variety of artificial metalloenzymes for non-natural reactions. However, many metal cofactors are inhibited by cellular components and therefore require purification of the scaffold protein. This limits the throughput of genetic optimization schemes applied to artificial m...
Organic Letters, 2010
5-Hydroxymethylcytosine (5-HOMe dC) was recently discovered as the sixth base in the mammalian ge... more 5-Hydroxymethylcytosine (5-HOMe dC) was recently discovered as the sixth base in the mammalian genome. The development of a new phosphoramidite building block is reported, which allows efficient synthesis of 5-HOMe dC containing DNA. Key steps of the synthesis are a palladium-catalyzed formylation and the simultaneous protection of a hydroxyl and amino group as a cyclic carbamate. DNA synthesis is possible under standard conditions, and deprotection can be carried out with dilute NaOH.
ChemMedChem, 2006
Inhibition of the enzyme catechol O-methyltransferase offers a therapeutic handle to regulate the... more Inhibition of the enzyme catechol O-methyltransferase offers a therapeutic handle to regulate the catabolism of catecholamine neurotransmitters, providing valuable assistance in the treatment of CNS disorders such as Parkinson's disease. A series of ribose-modified bisubstrate inhibitors of COMT featuring 2'-deoxy-, 3'-deoxy-, 2'-aminodeoxy-3'-deoxy-, and 2'-deoxy-3'-aminodeoxyribose-derived central moieties and analogues containing the carbocyclic skeleton of the natural product aristeromycin were synthesized and evaluated to investigate the molecular recognition properties of the ribose binding site in the enzyme. Key synthetic intermediates in the ribose-derived series were obtained by deoxygenative [1,2]-hydride shift rearrangement of adenosine derivatives; highlights in the synthesis of carbocyclic aristeromycin analogues include a diastereoselective cyclopropanation step and nucleobase introduction with a modified Mitsunobu protocol. In vitro biological evaluation and kinetic studies revealed dramatic effects of the ribose modification on binding affinity: 3'-deoxygenation of the ribose gave potent inhibitors (IC50 values in the nanomolar range), which stands in sharp contrast to the remarkable decrease in potency observed for 2'-deoxy derivatives (IC50 values in the micromolar range). Aminodeoxy analogues were only weakly active, whereas the change of the tetrahydrofuran skeleton to a carbocycle unexpectedly led to a complete loss of biological activity. These results confirm that the ribose structural unit of the bisubstrate inhibitors of COMT is a key element of molecular recognition and that modifications thereof are delicate and may lead to surprises.
Chemistry - A European Journal, 2010
Chemical Communications, 2009
Scheme 1 Photocleavage of single electron donor 1 to ketyl radical 2 and its conversion to the pr... more Scheme 1 Photocleavage of single electron donor 1 to ketyl radical 2 and its conversion to the products b-keto-amide 3 and b-hydroxylamide 4.
ChemBioChem, 2011
Quantum yields of up to 14 % for the formation of a long‐lived, charge‐separated state can be ach... more Quantum yields of up to 14 % for the formation of a long‐lived, charge‐separated state can be achieved in flavin‐capped DNA hairpins. The excited flavin state is quenched by electron‐transfer processes from adjacent DNA bases. The introduction of multiple (dG:dC) base pairs leads to efficient hole trapping that competes with the charge recombination through dA‐hopping processes.
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Papers by Christian Trindler