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.