A5044842810- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- Catalytic C–H Functionalization Methods
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Enzyme Catalysis and Immobilization
- Asymmetric Hydrogenation and Catalysis
- Synthesis and Catalytic Reactions
- Monoclonal and Polyclonal Antibodies Research
- Neurological diseases and metabolism
- Biochemical and Molecular Research
- Folate and B Vitamins Research
- Enzyme Structure and Function
- Microbial Metabolic Engineering and Bioproduction
- Porphyrin Metabolism and Disorders
- Antibiotic Resistance in Bacteria
- Chemical Reactions and Isotopes
- Electrochemical sensors and biosensors
- HER2/EGFR in Cancer Research
- Carbohydrate Chemistry and Synthesis
- Asymmetric Synthesis and Catalysis
- DNA and Nucleic Acid Chemistry
- Cyclopropane Reaction Mechanisms
- Cancer-related gene regulation
University of Manchester
2020-2024
Czech Academy of Sciences, Institute of Biotechnology
2020-2021
Cardiff University
2016-2019
The development of efficient and sustainable methods for the synthesis nitrogen heterocycles is an important goal chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds precursors. A potential biocatalytic approach this privileged scaffold would be asymmetric dearomatization readily assembled activated pyridines. However, nature yet yield a suitable biocatalyst specifically reaction. Here, by combining...
Abstract Chemo-selective modifications of proteins are fundamental to the advancement biological and pharmaceutical sciences. The search for biocompatible chemical reactions has prompted us investigate Horner–Wadsworth–Emmons (HWE) olefinations, iconic in organic synthesis that would give rise new selective protein olefinations. Our choice HWE olefinations was inspired by growing number methods generating aldehydes as transient reactive groups potential mild simple reaction conditions. Here...
There has been growing interest in performing organocatalysis within a supramolecular system as means of controlling reaction reactivity and stereoselectivity. Here, protein is used host for iminium catalysis. A pyrrolidine moiety covalently linked to biotin introduced the streptavidin organocatalytic activity. Whereas traditional systems stereoselectivity largely controlled by substituents added organocatalyst, enantiomeric enrichment reported completely host. Also, yield model increases...
NADP+-dependent enzymes are important in many biocatalytic processes to generate high-value chemicals for the pharmaceutical and food industry; hence, a cost-effective, efficient, environmentally friendly recycling system relatively expensive only marginally stable enzyme cofactor NADP+ offers significant benefits. regeneration schemes have previously been described, but their application is severely limited by low total turnover numbers (TTN) cofactor. Here, we report glutathione-based that...
The generation of immobilised oxidase biocatalysts allowing multifunctional oxidation valuable chemicals using molecular oxygen is described. Engineered galactose (GOase) variants M1 and M3-5, an engineered choline (AcCO6) monoamine (MAO-N D9) displayed long-term stability reusability over several weeks when covalently attached on a solid support, outperforming their free counterparts in terms (more than 20 fold), resistance to heat at 60 °C, tolerance neat organic solvents such as hexane...
Abstract There has been growing interest in performing organocatalysis within a supramolecular system as means of controlling reaction reactivity and stereoselectivity. Here, protein is used host for iminium catalysis. A pyrrolidine moiety covalently linked to biotin introduced the streptavidin organocatalytic activity. Whereas traditional systems stereoselectivity largely controlled by substituents added organocatalyst, enantiomeric enrichment reported completely host. Also, yield model...
Mammalian dihydrofolate reductases (DHFRs) catalyze the reduction of folate more efficiently than equivalent bacterial enzymes do, despite typically having similar efficiencies for their natural substrate, dihydrofolate. In contrast, we show here that DHFR from hyperthermophilic bacterium Thermotoga maritima can to tetrahydrofolate with an efficiency under saturating conditions. Nuclear magnetic resonance and mass spectrometry experiments showed no evidence production free during either...
The potential of antibody conjugates with high drug loading in anticancer therapy has recently been highlighted by the approval Trastuzumab deruxtecan and Sacituzumab govitecan. These biopharmaceutical approaches have spurred interest bioconjugation strategies defined degrees drug-to-antibody ratio (DAR), particular on native antibodies. Here, a glycoengineering methodology was developed to generate DAR up eight, combining highly selective enzymatic galactosylation oxidation biorthogonal...
Pterin-containing natural products have diverse functions in life, but an efficient and easy scheme for their vitro synthesis is not available. Here we report a chemoenzymatic 14-step, one-pot that can be used to generate 13C- 15N-labeled dihydrofolates (H2F) from glucose, guanine, p-aminobenzoyl-l-glutamic acid. This stands out previous approaches produce H2F the average yield of each step >91% it requires only single purification step. The use reaction allowed us overcome potential...
Selective acylation of the N-terminus over side-chains in peptides and proteins is a highly desirable but challenging reaction chemical biology. Here we report biomimetic approach using enzymatic situ activation carboxylic acids with ATP to generate reactive acyl-adenosine phosphates, which display high selectivity for N-termini proteins, including pharmaceutically relevant liraglutide, insulin glucagon. The tolerates range unsubstituted substituted fatty di-acids, thus making it suitable...
Hydride transfer is widespread in nature and has an essential role applied research. However, the mechanisms of how this transformation occurs living organisms remain a matter vigorous debate. Here, we examined dihydrofolate reductase (DHFR), enzyme that catalyzes hydride from C4' NADPH to C6 7,8-dihydrofolate (H2F). Despite many investigations mechanism reaction, contribution polarization π-bond H2F driving remains unclear. was stereospecifically labeled with deuterium β reacting center,...
Abstract A major challenge in chemical synthesis is to develop catalytic systems that convert simple molecules complex high-value products. Often these valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of molecule. Of great interest are enantioenriched amine diastereomers, which prevalent pharmaceuticals and agrochemicals, 1 yet preparation often relies low-efficiency multi-step synthesis. 2 Herein, we report discovery...
The conversion of carboxylic acids to thioesters is a key step in the biosynthesis natural products, resulting activation acyl groups for subsequent reactions, e.g. acylation nucleophiles including carbon-carbon bond formation. For example, Coenzyme A (CoA-SH; acetyl-S-CoA) are intermediates many metabolic pathways, and increasingly recognised as important cofactors epigenetic post-translational modifications, such N-, O- S-acylations proteins. However, limited availability broad range...
The conversion of carboxylic acids to thioesters is a key step in the biosynthesis natural products, resulting activation acyl groups for broad range subsequent biochemical reactions, such as acylations and alkylations. In particular, Coenzyme A (CoA-SH) play disproportionate roles many metabolic pathways, from fatty acids, polyketides peptides epigenetic post-translational modifications, N-, O- S-acylations proteins. However, lack access structurally diverse structural complexity CoA-SH...
Chemo-selective and site-specific modifications of proteins are fundamental to the advancement biological pharmaceutical sciences, from understanding basis cellular biology development biotherapeutics. Recent successes in bioconjugation chemistry have inspired search for more biocompatible chemical reactions, which has prompted us investigate Horner-Wadsworth-Emmons (HWE) olefinations, iconic reactions used widely organic synthesis that would give rise new selective protein olefinations. Our...
The conversion of carboxylic acids to thioesters is a key step in the biosynthesis natural products, resulting activation acyl groups for subsequent reactions, e.g. acylation nucleophiles including carbon-carbon bond formation. For example, Coenzyme A (CoA-SH; acetyl-S-CoA) are intermediates many metabolic pathways, and increasingly recognised as important cofactors epigenetic post-translational modifications, such N-, O- S-acylations proteins. However, limited availability broad range...
The development of efficient and sustainable methods for the synthesis nitrogen heterocycles is an important goal chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds precursors. A potential biocatalytic approach this privileged scaffold would be asymmetric dearomatization readily assembled activated pyridines. However, nature has yet yield a suitable biocatalyst specifically reaction. Here, by...
The potential of antibody conjugates with high drug loading in anticancer therapy has recently been highlighted by the approval Trastuzumab deruxtecan and Sacituzumab govitecan. These biopharmaceutical approaches have spurred interest bioconjugation strategies defined degrees antibody-to-drug (DAR) ratios, particular on native antibodies. Here we report a glycoengineering methodology to generate DAR up eight, combining highly selective enzymatic galactosylation oxidation biorthogonal tandem...
The development of efficient and sustainable methods for the synthesis nitrogen heterocycles is an important goal chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds precursors. A potential biocatalytic approach this privileged scaffold would be asymmetric dearomatization readily assembled activated pyridines. However, nature has yet yield a suitable biocatalyst specifically reaction. Here, by...