138108-37-9Relevant articles and documents
Mapping of the Modular Closthioamide Architecture Reveals Crucial Motifs of Polythioamide Antibiotics
Kloss, Florian,Chiriac, Alina Iulia,Hertweck, Christian
, p. 15451 - 15458 (2014)
Closthioamide, the first known secondary metabolite from an anaerobic microorganism (Clostridium cellulolyticum), represents a highly potent antibiotic that is active against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE) at nanomolar concentrations. To unveil structure-activity relationships of the unusual polythioamide natural product we have designed a synthetic grid to access analogues with altered terminal aromatic moieties, diverse p-phenyl substituents, different types and sizes of aliphatic spacers, varying numbers of thioamide residues, and diverse sizes and symmetries of the poly-β-thioalanyl backbone. A library of 28 closthioamide analogues was tested against a panel of human pathogenic bacteria. We found that aromatic terminal groups, the defined length of the spacer groups, the presence of all six thioamide residues and the modular arrangement of the β-thioalanyl units play essential roles for the antibiotic activity of closthioamide, yet there is a degree of freedom in the symmetry of the molecule. This study yields the first insights into pivotal structural motifs and the structural space of this new family of antibiotics, a prerequisite for the development of these promising antibiotics. Widening the scope: Structural motifs of closthioamide, the first antibiotic from strictly anaerobic microorganisms, were dissected and altered to unveil residues that are pivotal for antimicrobial activity. Using a modular approach, a library of 28 analogues was synthesized. First insights were gained into the structural space of this new family of antibiotics (see diagram).
Synthesis and structural study of cyclic 5-aminovaleric acid-linked β-Ala-β-Ala dipeptides
Mengel, Anne,Reiser, Oliver,Aube, Jeffrey
scheme or table, p. 5975 - 5977 (2009/05/31)
5-Aminovaleric acid and ornithine were evaluated as linkers for the cyclization of β-dipeptides. Two linked examples of β-Ala-β-Ala were prepared by standard coupling methods and their conformations probed by NMR, CD, and computational means. The data sug
Acetic acid derivatives
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, (2008/06/13)
Acetic acid derivatives of formula and hydrates, solvates and physiologically acceptable salts thereof are useful to inhibit the binding of adhesive proteins to blood platelets and also to inhibit blood platelet aggregation and cell-cell adhesion.
