A5068872012- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- International Science and Diplomacy
- Click Chemistry and Applications
- Organoselenium and organotellurium chemistry
- Chemical Synthesis and Analysis
- Fungal Biology and Applications
- Enzyme Catalysis and Immobilization
- Selenium in Biological Systems
- Phytochemistry and Bioactivity Studies
- Estrogen and related hormone effects
- Synthesis and Biological Evaluation
- Amino Acid Enzymes and Metabolism
- Cancer Risks and Factors
- Chemical Reactions and Isotopes
- Cholinesterase and Neurodegenerative Diseases
- Enzyme function and inhibition
- Enzyme Production and Characterization
- Peptidase Inhibition and Analysis
- Cancer survivorship and care
- Genomics and Chromatin Dynamics
- Polyamine Metabolism and Applications
- Microbial Metabolic Engineering and Bioproduction
- History and advancements in chemistry
- Protein Interaction Studies and Fluorescence Analysis
University of British Columbia
2024-2025
University of Bern
2021-2025
Sidney Kimmel Comprehensive Cancer Center
2020-2023
Statistics Collaborative
2023
Johns Hopkins Hospital
2020-2021
Johns Hopkins University
2021
University of Basel
2019-2020
University of Canterbury
2014-2017
Christchurch Clinical Studies Trust
2017
Christ University
2016
Abstract The conversion of sugars into glycomimetics typically involves multiple protecting‐group manipulations. development methodology allowing the direct aqueous free glycosides, and mimics oligosaccharides glycoconjugates in a high‐yielding stereoselective process is highly desirable. combined use 2‐azido‐1,3‐dimethylimidazolinium hexafluorophosphate Cu‐catalyzed Huisgen cycloaddition allowed synthesis range one‐step reaction directly from reducing under conditions. reaction, which...
Heterocyclic amines are a key structural motif for the synthesis of pharmaceuticals (e.g., antibiotics) as well pesticides and flavors. In this regard, imine reductases (IREDs) have recently emerged highly selective sustainable alternative asymmetric reductive amination reactions. Herein, we applied six IREDs, two which were newly identified, in reduction heterocyclic imines with either N, S, or O substitution at C-4. Since IREDs NADPH-dependent enzymes, commercially available, supported...
Selective acetylation of only the anomeric hydroxyl group unprotected sugars is possible in aqueous solution. This new one step route to glycosyl acetates may facilitate their use as donors for enzyme catalysed glycosylation.
Glycosyl thiols may be accessed from the corresponding reducing sugars in water without recourse to any sugar projecting groups by way of a DMC mediated reaction with thioacetic acid presence base, and hydrolysis anomeric thioacetate. produced this method used access glycoconjugates, such as glycopeptides use thiol-ene click reaction.
Abstract The N ‐α‐trimethyl 2‐selenohistidine selenoneine is the selenium isolog of natural antioxidant ergothioneine. Sulfur‐to‐selenium substitutions are known to endow proteins and nucleic acids with special activities. In contrast, secondary metabolites that exploit selenium‐specific chemistry rare. Selenoneine therefore provides a unique opportunity study how organoselenides interact cellular processes. this report we describe chemical synthesis other 2‐selenoimidazoles. With synthetic...
Treatment-associated symptoms drive early discontinuation of adjuvant endocrine therapy (ET) for breast cancer. We hypothesized that symptom monitoring with electronic patient-reported outcomes (ePROs) during ET will enhance detection, management, and persistence.
Ergothioneine is a sulfur-containing histidine derivative that emerges from microbial biosynthesis and enters the human body through intestinal uptake regulated distribution into specific tissues. Although proteins involved in are well characterized, less known about degradative pathways of ergothioneine. This report describes crystal structure active form ergothionase oral pathogen Treponema denticola complexed with substrate analogue desmethyl-ergothioneine sulfonic acid. enzyme catalyzes...
Abstract Ergothioneine is an emerging component of the redox homeostasis system in human cells and microbial pathogens, such as Mycobacterium tuberculosis Burkholderia pseudomallei . The synthesis stable isotope‐labeled ergothioneine derivatives may provide important tools for deciphering distribution, function, metabolism this compound vivo. We describe a general protocol production isotopologues with programmable 2 H, 15 N, 13 C, 34 S, 33 S isotope labeling patterns. This enzyme‐based...
Abstract The conversion of sugars into glycomimetics typically involves multiple protecting‐group manipulations. development methodology allowing the direct aqueous free glycosides, and mimics oligosaccharides glycoconjugates in a high‐yielding stereoselective process is highly desirable. combined use 2‐azido‐1,3‐dimethylimidazolinium hexafluorophosphate Cu‐catalyzed Huisgen cycloaddition allowed synthesis range one‐step reaction directly from reducing under conditions. reaction, which...
Weight gain after breast cancer poses health risks. We aimed to identify factors associated with weight during adjuvant endocrine therapy (AET).
Abstract Sulfoxide synthases are non‐heme iron enzymes that participate in the biosynthesis of thiohistidines, such as ergothioneine and ovothiol A. The sulfoxide synthase EgtB from Chloracidobacterium thermophilum ( Cth EgtB) catalyzes oxidative coupling between side chains N ‐α‐trimethyl histidine (TMH) cysteine (Cys) a reaction entails complete reduction molecular oxygen, carbon–sulfur (C−S) sulfur–oxygen (S−O) bond formation well carbon–hydrogen (C−H) cleavage. In this report, we show...
Mortality from triple negative breast cancer (TNBC) is significantly higher in African American (AA) women compared to White (WA) emphasizing ethnicity as a major risk factor; however, the molecular determinants that drive aggressive progression of AA-TNBC remain elusive. Here, we demonstrate for first time cells are inherently aggressive, exhibiting elevated growth, migration, and stem-like phenotype WA-TNBC cells. Meta-analysis RNA-sequencing data multiple AA- cell lines shows enrichment...
Abstract Ergothioneine is an emerging component of the redox homeostasis system in human cells and microbial pathogens, such as Mycobacterium tuberculosis Burkholderia pseudomallei . The synthesis stable isotope‐labeled ergothioneine derivatives may provide important tools for deciphering distribution, function, metabolism this compound vivo. We describe a general protocol production isotopologues with programmable 2 H, 15 N, 13 C, 34 S, 33 S isotope labeling patterns. This enzyme‐based...
Abstract Se‐benzyl selenoimidazolium salts are characterized by remarkable alkyl‐transfer potential under physiological conditions. Structure‐activity relationship studies show that selective monoalkylation of primary amines depends on supramolecular interactions between the selenoimidazole leaving group and target nucleophile. We demonstrate these reagents can be used for site‐selective nearly quantitative modification model protein lysozyme Lys13, bypassing higher intrinsic reactivities...
Summary The human health implications of exposure to environmental pollutants and food components (e.g. phytoestrogens) that mimic the female hormone 17β‐estradiol (xenoestrogens) are a subject significant debate. In this study, we use published data on dietary phytoestrogen intake sperm concentrations in USA China assess effects concentration as marker male reproductive health. Comparison trends shows has increased from 0.8 mg day −1 1993 13.7 2005 is trending down (not statistically...
In order to expand the toolbox of enzymes available for thioglycoside synthesis, we describe here first example an extremophilic glycosyl hydrolase from Halothermothrix orenii (HorGH1) engineered towards thioglycosynthase activity with a novel combination mutations. Using triple mutant, HorGH1 M299R/E166A/E354G, range thioglycosides fluoride donors and aromatic thiols could be synthesised exquisite stereoselectivity good excellent conversions (61-93%).
The interaction of unfractionated heparin (UFH) with universal reversal agent 7 (UHRA-7) is investigated. UHRA-7 composed a hyperbranched polyglycerol core onto which an array methylated tris(2-aminoethylamine) (Me-TREN) charged groups grafted, in turn are shielded layer small chain poly(ethylene glycol) methyl ether (mPEG) chains. This system has previously been shown to be biocompatible and effective at neutralizing heparin. binding constant Kb was determined from isothermal titration...
Given the rising number of multidrug-resistant (MDR) bacteria, there is a need to design synthetic antimicrobial peptides (AMPs) that are highly active, non-hemolytic, and soluble act as alternatives antibiotics either no longer effective or used drugs last resort. Machine learning tools allow straightforward in silico identification non-hemolytic peptides. Here, we utilized these rank best from two libraries: 1) 8192 with sequence bhxxbhbGAL, where b basic amino acid R K, h hydrophobic...
Abstract The N ‐α‐trimethyl 2‐selenohistidine selenoneine is the selenium isolog of natural antioxidant ergothioneine. Sulfur‐to‐selenium substitutions are known to endow proteins and nucleic acids with special activities. In contrast, secondary metabolites that exploit selenium‐specific chemistry rare. Selenoneine therefore provides a unique opportunity study how organoselenides interact cellular processes. this report we describe chemical synthesis other 2‐selenoimidazoles. With synthetic...
12053 Background: In the prospective POWER-remote trial, 51% and 12% of overweight/obese breast cancer survivors randomized to either a remotely delivered behavioral intervention or self-directed approach, respectively, lost ≥5% baseline weight. We collected patient-reported outcomes (PROs) examine impact >5% weight loss on symptoms, physical function (PF), wellbeing. hypothesized priori that, regardless study arm, those with would have improved PF at 6 months v. who did not. Methods:...
Abstract Glycosylation of bioactive molecules has been found to improve the pharmacokinetic properties parent molecule. However, their syntheses often require tedious protecting group manipulations. The development methodologies which allow direct aqueous conversion unprotected sugars into glycosides is therefore an ambitious goal. Herein, we present a broadly applicable method for synthesis selenoglycosides in water. We show ease conjugation glycosyl diselenides with various biomolecules,...
The development of a procedure for the one-pot synthesis glycosyl benzoates directly from unprotected sugars in aqueous media using 2-chloro-1,3-dimethylimidazolium chloride (DMC), thiobenzoic acid, and triethylamine is reported. These donors are excellent substrates wild-type mutant glycosidases. β-Glucosyl benzoate was hydrolysed by GH1 β-glucosidase derived Halothermothrix orenii (HorGH1). Subsequent use this substrate thioligase-mediated glycosylation p-nitrothiophenol demonstrated their...