title: Dissecting the structure of thiopeptides: assessment of thiazoline and tail moieties of baringolin and antibacterial activity optimization.
abstract: Several analogues of baringolin (1) were prepared to evaluate the role of its characteristic thiazoline ring and pentapeptidic tail with the aim of defining structure-activity relationships for these moieties. The thiazoline ring appeared as a crucial moiety to maintain a broad scope of activities against different Gram-positive bacteria. Further modifications were performed to simplify the structure of the natural product and assess the role of its tail, resulting in an enhanced in vitro performance. Analogue 25, with the thiazole-containing macrocycle and a 4-aminocyclohexane-1-carboxylic acid moiety in place of the pentapeptidic tail, was identified as a much more potent analogue, capable of overcoming the absence of the thiazoline ring and performing extraordinarily well against all strains tested. This is the first library of thiopeptide analogues produced by chemical synthesis alone, which demonstrates the robustness and convenience of the synthetic strategy used.
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Just-Baringo
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruno
authors.forename: Cristina
authors.initials: C
authors.lastname: Pitart
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Mercedes
authors.initials: M
authors.lastname: Álvarez
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; D013844:Thiazoles; C583833:baringolin