Modular syntheses of the glycosylphosphatidylinositol anchors of Toxoplasma gondii using a highly convergent strategy are reported.
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Synthesis of Glycosylphosphatidylinositol Analogues with an Unnatural -D-Glucosamine-(1→6)--Inositol Motif.
J Carbohydr Chem
April 2024
Department of Chemistry, University of Florida, 214 Leigh Hall, Gainesville, FL 32611, USA.
Glycosylphosphatidylinositol (GPI) anchors contain a unique α-D-glucosamine-(1→6)--inositol [αGlcN(1,6)Ins] motif in their conserved core structure. To facilitate investigations of the functional roles of this structural motif, two GPI analogues containing unnatural βGlcN(1,6)Ins, instead of αGlcN(1,6)Ins, and an alkyne group at different positions of the GPI core were designed and synthesized. To this end, an orthogonally protected pseudopentasaccharide derivative of GPIs with the βGlcN(1,6)Ins motif was convergently constructed via [3+2] glycosylation and used as the common intermediate to prepare both GPI analogues by streamlined synthetic protocols.
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Biomedicines
December 2024
Diagnostic and Interventional Neuroradiology Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
The glycosylphosphatidylinositol (GPI) is a glycol-lipid that anchors several proteins to the cell surface. The GPI-anchor pathway is crucial for the correct function of proteins involved in cell function, and it is fundamental in early neurogenesis and neural development. The PIG gene family is a group of genes involved in this pathway with six genes identified so far, and defects in these genes are associated with a rare inborn metabolic disorder manifesting with a spectrum of clinical phenotypes in newborns and children.
View Article and Find Full Text PDFGPLD1+ cancer stem cells contribute to chemotherapy resistance and tumor relapse in intestinal cancer.
J Biochem
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Laboratory of Anticancer Strategies, Advanced Research Initiative, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Article Synopsis
- Cancer stem cells (CSCs) are crucial in cancer growth and resistance, and recent research has identified GPLD1 as a marker for slowly cycling CSCs using a mouse intestinal cancer model.
- Inhibiting GPLD1, particularly combined with the chemotherapy drug 5-fluorouracil, significantly reduces cancer cell viability and prevents tumor regrowth in organoids.
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Topological confinement by a membrane anchor suppresses phase separation into protein aggregates: Implications for prion diseases.
Proc Natl Acad Sci U S A
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Department Biochemistry of Neurodegenerative Diseases, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum 44801, Germany.
Protein misfolding and aggregation are a hallmark of various neurodegenerative disorders. However, the underlying mechanisms driving protein misfolding in the cellular context are incompletely understood. Here, we show that the two-dimensional confinement imposed by a membrane anchor stabilizes the native protein conformation and suppresses liquid-liquid phase separation (LLPS) and protein aggregation.
View Article and Find Full Text PDFThe good, the bad, and the hazardous: comparative genomic analysis unveils cell wall features in the pathogen Candidozyma auris typical for both baker's yeast and Candida.
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Institute for Biomedicine, ETSIAMB, University of Castilla-La Mancha, 02008 Albacete, Spain.
The drug-resistant pathogenic yeast Candidozyma auris (formerly named Candida auris) is considered a critical health problem of global importance. As the cell wall plays a crucial role in pathobiology, here we performed a detailed bioinformatic analysis of its biosynthesis in C. auris and related Candidozyma haemuli complex species using Candida albicans and Saccharomyces cerevisiae as references.
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