Biological activities of isolated tunicamycin and streptovirudin fractions

Abstract

The nucleoside antibiotics tunicamycin and streptovirudin were separated by high-performance liquid chromatography into a series of 256-nm-absorbing peaks. Most of the streptovirudin peaks eluted from a Biosil ODS column earlier than those of tunicamycin, indicating that they were less hydrophobic. With the exception of the first peak, 17 other tunicamycin peaks were potent inhibitors of the formation of dolichylpyrophosphoryl-N-acetylglucosamine with 50% inhibition of the solubilized GlcNAc-1-P transferase requiring about 10 ng of antibiotic per mL. These fractions also inhibited the synthesis of dolichylphosphorylglucose, but in these cases about 500 ng/mL was necessary to achieve 50% inhibition. In MDCK cells in culture, the four major tunicamycin peaks inhibited the incorporation of [2-(3)H]mannose into protein by 50% at about 0.2-0.5 microgram/mL, but [3H]leucine incorporation into protein was unaffected, except at high levels of antibiotic (5-10 microgram/mL). Essentially the same results were observed with the streptovirudin fractions except that they were somewhat less active and some inhibition of protein synthesis was observed with several of these peaks.

Synergistic killing of FLT3ITD-positive AML cells by combined inhibition of tyrosine-kinase activity and N-glycosylation

“…A possible reason for selective inhibition of FLT3ITD-positive cells by compounds affecting glycosylation may be a further shift of FLT3ITD towards the intracellular localization, thereby abrogating signaling from the cell surface and in turn cell transformation. Tunicamycin is a bacterial antibiotic, which specifically inhibits the transfer of activated sugars to dolicholphosphate, an essential step in N-glycosylation of proteins at the ER [11, 12]. Because of the fundamental role of this process, tunicamycin has cytotoxic potential, but at low or moderate doses, more specific effects on different cell types have been observed.…”

Liquid Chromatography–Electrospray Mass Spectrometry of Tunicamycin-Type Antibiotics

“…These components, which they named A 0 , A 1 , A 2 , B 1 , B 2 , C 1 , C 2 , D 1 , and D 2 are identical with Ito's designations I, II, III, IV, V, VII, IX, and X, respectively. Several minor components, A 3 , A 4 , B 3 , B 4 , B 5 , B 6 , and C 3 , were also observed but were not structurally assigned. Using a 1:2 acetonitrile:water solvent system Eckardt et al separated the tunicamycin complex into six peaks, the fourth peak of which was the major component (17).…”

“…Mycospocidins (from S. bobiliae) (4), streptovirudins (S. griseoflavus sp. thuringiensis) (5,6), and antibiotics MM 19290 (S. clavuligerus) and 24010 (from an unidentified streptomycete) (7,8) have also been described that are structurally akin to the tunicamycins, differing in the Nacyl moiety and/or substitution of 5,6-dihydrouracil for the uracil group. The corynetoxins are unusual in that they are produced by a coryneform bacterium that is highly divergent from the streptomycetes, and then only in association with a specific phage (9,10).…”

The biochemical and ultrastructural effects of tunicamycin and D‐glucosamine in L1210 leukemic cells

“…Tunicamycin (TM) represents a family of closely related antibiotics containing N-acetylglucosamine, a novel 11-carbon sugar tunicamine, a uracil moiety, and a fatty acid residue which, by virtue of its microheterogeneity, gives rise to the physically distinct (Ito et al, 1980) but biochemically similar (Keenan et al, 1981) components within this class of agents. Tunicamycin specifically inhibits the initial biosynthetic step in the assembly of dolichol-linked oligosaccharides (Tkacz and Lampen, 1975;Heifetz et al, 1979) and, accordingly, this antibiotic has been employed in attempts to elucidate the role of asparagine-linked glycoprotein synthesis in secretory processes (Hickman et al, 1977;Struck et al, 19781, plasma membrane turnover (Olden c:t al., 1978;Damsky et al, 19791, tumor cell immunogenicity (Morin and Bernacki, 1979), and metastasis (Irimura et al, 1981).…”