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Structure and biological activity of ascamycin, a new nucleoside antibiotic

TLDR
Remarkable selective toxicity of ascamycin compared to the dealanyl derivative was accounted for on the basis of a dealanylating enzyme present in the envelope of sensitive bacteria.
Abstract
A newly isolated strain of Streptomyces sp. produces a new nucleoside antibiotic, ascamycin and the corresponding dealanyl derivative. The structure of ascamycin was determined to be 2-chloro-9-beta-[5-O-(N-L-alanyl)sulfamoyl-D-ribofuranosyl]-adenine. Remarkable selective toxicity of ascamycin compared to the dealanyl derivative was accounted for on the basis of a dealanylating enzyme present in the envelope of sensitive bacteria. After dealanylation, it becomes permeable to cell membrane.

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Inhibition of the D-alanine:D-alanyl carrier protein ligase from Bacillus subtilis increases the bacterium's susceptibility to antibiotics that target the cell wall.

TL;DR: An inhibitor is designed (d‐alanylacyl‐sulfamoyl‐adenosine), which is able to block the d‐Ala adenylation by DltA at a Ki value of 232 nmin vitro and a significant inhibition of growth for different Bacillus subtilis strains when the inhibitor is used in combination with vancomycin.
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Trapping interactions between catalytic domains and carrier proteins of modular biosynthetic enzymes with chemical probes

TL;DR: The design and implementation of the chemical tools that have proven to be useful in biochemical and biophysical studies of these natural product biosynthetic enzymes are described.
Patent

Aminoacyl sulfamides for the treatment of hyperproliferative disorders

TL;DR: In this article, aminoacyl sulfamides are described for the treatment of hyperproliferative disorders, specifically psoriasis, and 5'-deoxy-adenosine 5'-N(N-L-phenylalanyl)sulfamide and 5'deoxy-(n-L)-tryptophanyl sulfamide.
Journal ArticleDOI

Enhanced Production of the Fluorinated Nucleoside Antibiotic Nucleocidin by a rifR-Resistant Mutant of Streptomyces calvus IFO13200

TL;DR: To activate the dormant secondary metabolism of S. calvus, the effect of an rpoB mutation that was induced by ultraviolet light irradiation showed remarkably improved antibiotic activity, which was extracted by n-butanol and identified by Electron-Spray-Ionization Mass Spectrometry.
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