Antibiotics with new mechanisms of action are urgently required to combat the growing health threat posed by resistant pathogenic microorganisms. We synthesized a family of peptidomimetic antibiotics, based on the antimicrobial peptide protegrin I. Several rounds of optimization gave a lead compound that was active in the nanomolar range against gram-negative Pseudomonas sp., but was largely inactive against other Gram-negative and Gram-positive bacteria. Biochemical and genetic studies showed the peptidomimetics had a non-membrane-lytic mechanism of action and identified a homologue of the ß-barrel protein LptD (Imp/OstA), which functions in outer membrane biogenesis, as a cellular target. The peptidomimetic showed potent antimicrobial activity in a mouse septicemia infection model. Drug-resistant strains of Pseudomonas are a serious health problem, so this family of antibiotics may have important therapeutic applications. A synthesized antibiotic targets a protein involved in outer membrane biogenesis to selectively kill Pseudomonas pathogens. 1 Peptidomimetic Antibiotics Target Outer Membrane Biogenesis in Pseudomonas aeruginosa AbstractAntibiotics with new mechanisms of action are urgently required to combat the growing health

A novel biocatalytic protocol for CC bond formation is described and is an equivalent to Friedel–Crafts alkylation. S‐Adenosyl‐L‐methionine (SAM), the major methyl donor for biological methylation catalyzed by methyltransferases (Mtases), can perform alkylations (see scheme). These enzymes can accept non‐natural cofactors and transfer functionalities other than methyl onto aromatic substrates.

Iminosugars, featuring a basic nitrogen at the hetero atom position in carbohydrate rings, gain increasing interest in the search for novel approaches towards cancer drug development. This compound class is known as competitive inhibitors of carbohydrate manipulation enzymes, such as glycosidases, which are involved in tumor cell invasion and migration. Such enzymes are also responsible for the attachment of oligosaccharides to the cell surface of tumor cells, displayed as glycoproteins, glycolipids, and proteoglycans, which play an important role in malignant phenotype and tumor growth. Furthermore, cancer cells show an extremely active lysosomal system which is reflected by enhancement of glycoprotein turnover. Iminosugars were found to interact with glycosyl hydrolases responsible for this kind of action in cancer cells and thus open a new compound class in the research field of finding new anti-cancer activities. This review will focus on the role of iminosugars in cancer therapy and will give an overview of their properties.

Eine neuartige biokatalytische C‐C‐Verknüpfung, die äquivalent zur Friedel‐Crafts‐Alkylierung ist, wird vorgestellt. S‐Adenosyl‐L‐methionin (SAM), der Haupt‐Methyldonor bei Methyltransferase(Mtase)‐katalysierten biologischen Methylierungen, kann Alkylierungen bewirken (siehe Schema). Diese Enzyme akzeptieren nichtnatürliche Cofaktoren und können andere Funktionalitäten als Me auf aromatische Substrate übertragen.

A chemoenzymatic, asymmetric total synthesis of the antibiotic (R)-fridamycin E has been accomplished following a biocatalytic deracemization procotol. The key step comprises the construction of the chiral side-chain from a functionalized rac-2,2-disubstituted oxirane via a kinetic resolution/stereo-