Sugar analogs are versatile chemical tools for probing or inhibiting glycan functions. However, chemical tools are insufficient for glycosaminoglycans (GAGs), which play crucial roles in various biological processes, such as extracellular matrix formation and growth factor signaling. To develop a new compound for detecting GAGs or manipulating GAG functions, we chemically synthesized 2-azide-xylose (2-Az-Xyl), an azide-type analog of Xyl that is a component of the common linkage tetrasaccharide in GAGs, and explored its application to biological experiments. Treatment of cultured cells with 2-Az-Xyl inhibited cell proliferation and reduced the levels of GAGs, particularly heparan sulfate (HS). Although this sugar analog did not perturb the biosynthesis of nucleotide sugars and expression of the key enzymes for HS biosynthesis, 2-Az-Xyl directly inhibited the activity of XYLT2, an initial enzyme for GAG biosynthesis, indicating that 2-Az-Xyl directly inhibits GAG biosynthesis. These findings suggest that 2-Az-Xyl inhibits cell proliferation by blocking GAG biosynthesis through inhibiting XYLT2 activity.
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http://dx.doi.org/10.1016/j.bbrc.2024.151083 | DOI Listing |
Mol Biol (Mosk)
December 2024
Gamaleya Federal Research Center of Epidemiology and Microbiology, Moscow, 123098 Russia.
Previously obtained highly immunogenic Env-VLPs ensure overcoming the natural resistance of HIV-1 surface proteins associated with their low level of incorporation and inaccessibility of conserved epitopes to induce neutralizing antibodies. We also adopted this technology to modify Env trimers of the ZM53(T/F) strain to produce Env-VLPs by recombinant vaccinia viruses (rVVs). For VLP production, rVVs expressing Env, Gag-Pol (HIV-1/SIV), and the cowpox virus hr gene, which overcomes the restriction of vaccinia virus replication in CHO cells, were used.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Faculty of Biology, Moscow State University, Moscow, 119234 Russia.
As a result of molecular domestication of the gag gene of errantiviruses, the Gagr gene was formed in the genome of Drosophila melanogaster. It has previously been shown that the Gagr gene is transcribed at the highest level in gut tissues relative to other tissues, and its transcription is most effectively induced in females in response to ammonium persulfate added to the nutrient medium. In the present work, the gut transcriptome of females with knockdown of the Gagr gene was studied in all tissues under standard conditions and under stress conditions caused by ammonium persulfate.
View Article and Find Full Text PDFObjective: Aim: To improve the treatment results of patients with anastomotic leaks by studying genetic predisposition.
Patients And Methods: Materials and Methods: The object of this prospective study were 17 patients with anastomotic leaks. A group of 80 practically healthy people was tested as control.
Mol Genet Metab
November 2024
Departments of Chemistry, University of Washington, Seattle, WA 98195, USA. Electronic address:
Measurement of enzymatic activity in newborn dried blood spots (DBS) is the preferred first-tier method in newborn screening (NBS) for mucopolysaccharidosis (MPS) disorders. However, false positives are observed due mainly to the presence of pseudodeficiencies. Our previous publications on glycosaminoglycan (GAG) biomarker levels in dried blood spots (DBS) for mucopolysaccharidoses demonstrated that second-tier GAG biomarker analysis can dramatically reduce the false positive rate in NBS.
View Article and Find Full Text PDFAnal Chim Acta
January 2025
Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeong-buk, 37673, Republic of Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeong-buk, 37673, Republic of Korea. Electronic address:
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