Of tunicamycins

Scheme 18. Silicon-directed radical cyclization in Myers s synthesis of (+)-tunicamycin V (97).

Methylene sugars are versatile starting compounds for the synthesis of aromatic and hydroxymethyl C-glycosyl compounds (71) and of double-ended C-glycosyl compounds (70). The double bond undergoes 1,3-dipolar cycloadditions to give isoxazoline derivatives (71), such as that used as a model for the synthesis of tunicamycin. Also, reaction with iodonium sym-... 

Secretion of nonglycosylated macromolecules in the presence of tunicamycin has also been investigated in a number of other cells. Rat-liver cell-secretion ol albumin (a carbohydrate-free protein), transferrin, and a-acid glycoprotein was not inhibited, and, in chick-liver cells, only a decrease by 10-25% in the secretion of transferrin and the apoprotein B chain of very-low-density lipoprotein was noted.463,464 The secretion of ovalbumin (a glycoprotein) from hen oviduct was not blocked by tunicamycin.465... 

The diminution in infectivity could be caused either by the production of virus particles having a lessened or abolished infectivity, or a decreased formation of infectious virions. The envelope glycoproteins of Semliki Forest virus and Sindbis virus synthesized in the presence of tunicamycin (and, thus, devoid of carbohydrate) are metabolically stable. They do not participate in the assembly of virus particles, although nucleocapsids are still formed under these conditions and are... 

The fact that earlier investigations of the effect of tunicamycin on the replication of Rous sarcoma virus failed to show the unglvcosyl-... 

Cultured BHK cells that had heen maintained in a medium containing tunicamycin still shed various membrane glycoproteins into the medium,539 and this is in keeping with observations mentioned in Section IV,4. However, the proportion of fibronectin found in the medium appeared to he lessened.540-541 Cells kept in the presence of tunicamycin showed profound morphological changes, from epitheloid to elongated, spindle-shaped morphology, and lowered adhesion to the substratum. 

For certain aspects of work with cell cultures, a useful property of tunicamycin is that it can be used to synchronize cell division. After release of the block imposed hv the drug, the cloning efficiency was also higher, and the cloning size more regular, than in the control culture.547... 

Human-leukemic antigen (HLA-DR) has been found in remarkably low proportions on the plasma membrane of human, lymphoblastoid cells. In the presence of tunicamycin, both subunits of this cell-surface antigen showed lower apparent molecular weights. One of them completely lost its [3H]-labelled 2-acetamido-2-deoxy-D-glucose portion, implying that HLA-DR antigens possess oligosaccharides whose synthesis is lipid carrier-dependent.555... 

A special example of cell-cell interaction is the adherence of group B streptococci to canine, epithelial cells that are infected with influenza A virus. However, this capacity was blocked in the presence of tunicamycin, and this result supports the concept that adherence of streptococci to mammalian cells involves recognition of viral hemagglutinin, or its carbohydrate complement, the synthesis of which is blocked by tunicamycin.556... 

The biosynthesis in yeast of two enzymes that are D-mannoproteins has been studied. A membrane-associated isozyme of invertase (EC 3.2.1.26) has been shown to be a precursor of the external invertase.190 Its molecular weight, as determined by SDS-poly(acrylamide) gel electrophoresis, is 50,000, that is, smaller than that of the external invertase, and it correlates well with the presence of only the inner-core sugars of the final form. It is strictly bound to membranes, possibly those of the endoplasmic reticulum, and it can be completely split191 by endo-/3-N-acetylglucosaminidase H (EC 3.2.1.30). The addition of tunicamycin, which specifically inhibits formation of d-GIcNAc-PP-DoI, inhibits synthesis of external invertase, as well as further formation of the membrane-associated form, which completely disappears after addition of the antibiotic.190 In these aspects, the synthesis of this extracellular enzyme follows the pathway for secreted glycoproteins in animal systems. 

To examine whether unglycosylated acid carboxypeptidase can secreted into the medium, we assayed medium in the presence or absence of tunicamycin by Western blotting analysis. The results indicate that the acid carboxypeptidase was not secreted into the culture medium when tunicamycin was added (Figure 26 B). This suggests that the decrease of enzymatic activity in culture filtrates of mycelia grown in the presence of tunicamycin is largely owing to the decrease of the concentration of the enzyme. 

Sandin RL, Rogers AL, Patterson RJ, Beneke ES Evidence of mannose-related adherence of Candida albicans to human buccal epithelial cells in vitro. Infect Immun 1982 35 79-85. Douglas LJ, McCourtie J Effect of tunicamycin treatment on the adherence of Candida albicans to human buccal epithelial cells. FEMS Microbiol Lett 1983 16 199-202. 

Delom, F., Emadali, A., Cocolakis, E., Lebmn, J.J., Nantel, A. and Chevet, E. (2007) Calnexin-dependent regulation of tunicamycin-induced apoptosis in breast carcinoma MCF-7 cells. Cell Death Differ. 74(3), 586-596. 

Irimura, T., Gonzales, R. and Nicolson, G. L. (1981). Effects of tunicamycin on metastatic B16 melanoma cell surface glycoproteins and blood-borne arrest and survival properties. Cancer Res. 41, 3411-3418. 

One of the early applications was the screening of a library of 233 heterozygous deletion strains in a pooled format to identify the target of tunicamycin... 

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