The surface charge as well as the electrochemical properties and ligand binding abilities of the Gram‐positive cell wall is controlled by the d‐alanylation of the lipoteichoic acid. The incorporation of d‐Ala into lipoteichoic acid requires the d‐alanine:d‐alanyl carrier protein ligase (DltA) and the carrier protein (DltC). We have heterologously expressed, purified, and assayed the substrate selectivity of the recombinant proteins DltA with its substrate DltC. We found that apo‐DltC is recognized by both endogenous 4′‐phosphopantetheinyl transferases AcpS and Sfp. After the biochemical characterization of DltA and DltC, we designed an inhibitor (d‐alanylacyl‐sulfamoyl‐adenosine), which is able to block the d‐Ala adenylation by DltA at a Ki value of 232 nmin vitro. We also performed in vivo studies and determined a significant inhibition of growth for different Bacillus subtilis strains when the inhibitor is used in combination with vancomycin.
A key to the development of new antibiotics with increased efficiency can be found in (E)‐alkene dipeptide isosteres. Here we report on the incorporation of such a dipeptide isostere into a linear peptide precursor by chemical synthesis in combination with enzymatic cyclisation.
[structure: see text] An efficient total synthesis of the annonaceous acetogenin jimenezin was achieved. The key steps used were a highly stereoselective intramolecular allylboration to establish the tetrahydropyran ring and an intramolecular Williamson reaction to close the tetrahydrofuran ring.
Peptides U 0400First Stereoselective Synthesis of a Pro-Pro E-Alkene Dipeptide Isostere. -The diastereoselective alkenylation of L-proline derived aldehyde (II) and the stereoselective Ireland-Claisen rearrangement of the siloxy acetate (VI) are the highlights in the preparation of Fmoc-protected proline-proline E-alkene isostere (IX). -(BANDUR, N. G.; HARMS, K.; KOERT*, U.; Synlett 2005, 5, 773-776; Fachbereich Chem., Philipps-Univ., D-35043 Marburg, Germany; Eng.) -R. Staver 33-229
The stereoselective syntheses of a Tyr-Tyr and a Pro-Pro E-alkene isostere are described. While the Tyr-Tyr isostere was synthesized following a convergent olefination strategy, the trisubstituted E-configured double bond of the Pro-Pro isostere was generated by an Ireland-Claisen rearrangement. The configuration of all key intermediates containing new stereocenters was determined by X-ray crystallography.
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