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An oligosaccharides library of small tri- and tetrasaccharides is prepared by one-pot sequential glycosylation strategies using thioglycosides as glycosylation reagents. The methodology facilitates rapid assembly of 33 linear or branched protected oligosaccharides.

O -GlcNAcylation is a post-translational modification that links metabolism with signal transduction. High O -GlcNAcylation appears to be a general characteristic of cancer cells. It promotes the invasion, metastasis, proliferation and survival of tumor cells, and alters many metabolic pathways. Glycogen metabolism increases in a wide variety of tumors, suggesting that it is an important aspect of cancer pathophysiology. Herein we focused on the O -GlcNAcylation of liver glycogen phosphorylase (PYGL)—an important catabolism enzyme in the glycogen metabolism pathway. PYGL expressed in both HEK 293T and HCT116 was modified by O -GlcNAc. And both PYGL O -GlcNAcylation and phosphorylation of Ser15 (pSer15) were decreased under glucose and insulin, whereas increased under glucagon and Na2S2O4 (hypoxia) conditions. Then, we identified the major O -GlcNAcylation site to be Ser430, and demonstrated that pSer15 and Ser430 O -GlcNAcylation were mutually reinforced. Lastly, we found that Ser430 O -GlcNAcylation was fundamental for PYGL activity. Thus, O -GlcNAcylation of PYGL positively regulated pSer15 and therefore its enzymatic activity. Our results provided another molecular insight into the intricate post-translational regulation network of PYGL. [ABSTRACT FROM AUTHOR]

A novel method for the synthesis of unsymmetrically 3,4-disubstituted thiophenes was developed based on the intermolecular thiazole-alkyne Diels-Alder reactions involving 3,4-bis(trimethylsilyl)thiophene. The synthetic strategy was characterized by the formation of the [2+2]- and [4+2]-cycloaddition adducts of 3,4-didehydrothiophene via 1,3-dipolar cycloadditions. Furthermore, the synthetic process was characterized by 3,4-bromothiophene modification and intermolecular thiazole-alkyne Diels-Alder reactions with 3,4-bis(trimethylsilyl)thiophene.

Lymphocyte infiltration is an important feature of cancer. There is a complex network of chemokines that influence the degree and phenotype of lymphocyte infiltration, as well as the growth, survival, migration, and angiogenesis of tumor cells. High heterogeneity metastasis is a major obstacle to the treatment of breast cancer. Herein, we showed that O-GlcNAcylation of B lymphocyte-induced maturation protein-1 (Blimp-1) in lymphocytes inhibited the migration and invasion of breast cancer cells. It was found that Blimp-1 O-GlcNAcylation at Ser448 and Ser472 in lymphocytes promoted its nuclear localization, and blocked the bindings to three regions upstream of the ccl3l1 promoter to inhibit its expression. Decreased expression of CCL3L1 in lymphocytes not only decreased CCR5 expression in breast cancer cells, but also inhibited the membrane localization and activation of CCR5, thus blocking the migration and invasion of breast cancer cells in vitro. Therefore, O-GlcNAcylation of Blimp-1 in lymphocytes may serve as a new target for the treatment of metastatic breast cancer., Implications: This study reveals a new mechanism by which the lymphatic system promotes breast cancer cell metastasis., (©2021 American Association for Cancer Research.)

The glycan portion of ganglioside HLG-2, which was identified in the extracts of the sea cucumber Holothuria leucospilota , was synthesized in a highly efficient and stereoselective manner. The unusual sequence of the trisaccharide moiety, α-N-glycolylsialyl-(2,4)-α-N-acetylsialyl-(2,6)-glucoside, was assembled by stereoselective coupling of a 5-N,4-O-carbonyl-protected sialyl phosphate donor, a N-2,2,2-trichloroethoxycarbonyl (Troc)-protected sialyl acceptor, and a (trimethylsilyl)ethyl-β-glucosyl acceptor in high yield. The synthesis featured the high-yielding construction of two α-sialyl linkages.