Efficient methodologies for synthesizing enantiopure α-deuterated derivatives of serine, cysteine, selenocysteine, and 2,3-diaminopropanoic acid have been developed. H/D exchange was achieved by deprotonation of a chiral bicyclic serine equivalent followed by selective deuteration. Additionally, diastereoselective additions of thiols, selenols, and amines to a chiral bicyclic dehydroalanine in deuterated alcohols allowed site-selective deuteration at the Cα atom of cysteine, selenocysteine, and 2,3-diaminopropanoic acid derivatives. A deuterated analogue of carbocysteine, a drug for the treatment of bronchiectasis, was synthesized.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.orglett.2c02715 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Se-methylselenocysteine Inhibits Migration and Glycolysis in Anaplastic Thyroid Carcinoma Cells via the ERK1/2 Signaling Pathway .
Ann Clin Lab Sci
November 2024
Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
Objective: The aim of the present study was to determine the effects of selenium-methylselenocysteine (MSC) on the viability, migration, and glycolysis of human ATC cell lines 8305 and BHT101 .
Methods: Cells were treated with MSC and viability was determined using the Cell Counting Kit 8 assay. The migratory ability of cells was detected using a Transwell migration assay, and the expression levels of proteins involved in the ERK1/2, JNK, and p38 signaling pathways were measured by western blotting.
Use of laser-ablation inductively-coupled mass spectroscopy for analysis of selenosugars bound to proteins.
Metallomics
January 2025
Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706, USA.
We previously used high pressure liquid chromatography (HPLC) coupled with Se-specific inductively coupled plasma mass spectrometry (ICP-MS) and molecule specific (ESI Orbitrap MS/MS) detection to study the increase in liver Se in turkeys and rats supplemented as selenite in high-Se (5 µg Se/g diet) and adequate-Se diets. We found that far more Se is present as selenosugar (seleno-N-acetyl galactosamine) than is present as selenocysteine (Sec) in true selenoproteins. In high-Se liver, the increase in liver Se was due to low molecular weight (LMW) selenometabolites as glutathione-, cysteine- and methyl-conjugates of the selenosugar, but also as high molecular weight (HMW) species as selenosugars decorating general proteins via mixed-disulfide bonds.
View Article and Find Full Text PDFNon-Canonical Cytochrome P450 Enzymes in Nature.
bioRxiv
December 2024
Department of Chemistry, Princeton University, Princeton, NJ, USA.
Cytochrome P450s (CYPs) are a superfamily of thiolate-ligated heme metalloenzymes principally responsible for the hydroxylation of unactivated C-H bonds. The lower-axial cysteine is an obligatory and universally conserved residue for the CYP enzyme class. Herein, we challenge this paradigm by systematically identifying non-canonical CYPs (ncCYPs) that do not harbor a cysteine ligand.
View Article and Find Full Text PDFSelenocysteine-Activatable Near-Infrared Fluorescent Probe for Screening of Anti-inflammatory Components in Herbs.
Anal Chem
January 2025
Pukou Hospital of Chinese Medicine Affiliated to China Pharmaceutical University, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Inflammation, a central process in numerous diseases, plays a crucial role in hepatic disorders, arthritis, cardiac conditions, and neurodegenerative ailments. Given the lack of effective anti-inflammatory drugs, it is imperative to assess inflammation severity and explore novel therapeutics. Selenocysteine (Sec), a key mediator of selenium's biological function, is closely involved in anti-inflammatory responses.
View Article and Find Full Text PDFEEFSEC deficiency: A selenopathy with early-onset neurodegeneration.
Am J Hum Genet
January 2025
Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany; Center for Rare Disease, University of Tübingen, 72076 Tübingen, Germany; Genomics for Health in Africa (GHA), Africa-Europe Cluster of Research Excellence (CoRE).
Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!