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Physicochemical Properties, Drug Release and In Situ Depot-Forming Behaviors of Alginate Hydrogel Containing Poorly Water-Soluble Aripiprazole.
Gels
November 2024
Department of Pharmacy, College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea.
The objective of this study was to investigate the physicochemical properties, drug release and in situ depot-forming behavior of alginate hydrogel containing poorly water-soluble aripiprazole (ARP) for achieving free-flowing injectability, clinically accessible gelation time and sustained drug release. The balanced ratio of pyridoxal phosphate (PLP) and glucono-delta-lactone (GDL) was crucial to modulate gelation time of the alginate solution in the presence of calcium carbonate. Our results demonstrated that the sol state alginate hydrogel before gelation was free-flowing, stable and readily injectable using a small 23 G needle.
View Article and Find Full Text PDFNon-standard amino acids (nsAAs) that are L-phenylalanine derivatives with aryl ring functionalization have long been harnessed in natural product synthesis, therapeutic peptide synthesis, and diverse applications of genetic code expansion. Yet, to date these chiral molecules have often been the products of poorly enantioselective and environmentally harsh organic synthesis routes. Here, we reveal the broad specificity of multiple natural pyridoxal 5'-phosphate (PLP)-dependent enzymes, specifically an L-threonine transaldolase, a phenylserine dehydratase, and an aminotransferase, towards substrates that contain aryl side chains with diverse substitutions.
View Article and Find Full Text PDFStructure and identification of the native PLP synthase complex from lysate.
mBio
January 2025
Department of Microbiology, Immunology & Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA.
Many protein-protein interactions behave differently in biochemically purified forms as compared to their states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here, we apply the bottom-up structural proteomics method, , toward a model methanogenic archaeon.
View Article and Find Full Text PDFHPLC-MS/MS based method for the determination of 2-(3-hydroxy-5-phosphonooxymethyl-2-methyl-4-pyridyl)-1,3-thiazolidine-4-carboxylic acid in human plasma.
Sci Rep
October 2024
Faculty of Chemistry, Department of Environmental Chemistry, University of Lodz, 163/165 Pomorska Str., 90-236, Łódź, Poland.
Article Synopsis
- - The report introduces a new high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to measure a specific compound, HPPTCA, related to cysteine and vitamin B6, using 4-deoxypyridoxine as an internal standard.
- - Sample preparation includes extracting HPPTCA from plasma proteins with acetonitrile, followed by ultrafiltration and dilution before analysis; the separation process takes 6 minutes at a controlled temperature with a precise gradient elution.
- - The assay demonstrated linearity in measuring HPPTCA levels in plasma with a detection limit of 0.25 µmol/L, successfully confirming HPPTCA presence in samples from healthy donors with concentrations between
Elucidation of the stereochemical mechanism of cystathionine γ-lyase reveals how substrate specificity constrains catalysis.
ACS Catal
August 2024
Department of Biochemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
Pyridoxal phosphate (PLP)-dependent enzymes play essential roles in metabolism and have found applications for organic synthesis and as enzyme therapeutics. The vinylglycine ketimine (VGK) subfamily hosts a growing set of enzymes that play diverse roles in primary and secondary metabolism. However, the molecular determinates of substrate specificity and the complex acid-base chemistry that enables VGK catalysis remain enigmatic.
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