Synthesis and structure–activity relationship studies of teixobactin analogues

Abstract

A new series of teixobactin analogues were prepared using a convenient synthetic strategy and their antibacterial activities were evaluated.

Rational Design and Synthesis of Modified Teixobactin Analogues: In Vitro Antibacterial Activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa

“…Although the removal of the N ‐methyl group from N ‐Me‐ d ‐Phe 1 has a minimal effect on the potency, activity was lost when Wu et al. replaced d ‐Phe with d ‐Tyr . The same observation was obtained with analogue 69 , in which the phenyl group was substituted with an indole moiety; our ( d ‐Trp 1 ,Arg 10 ) analogue 69 is essentially inactive.…”

“…Teixobactin ( 1 ), comprised of a 13‐membered depsipeptide core and a tethered linear heptapeptide, offers multiple sites for synthetic modifications to improve its potency and efficacy. In less than three years since its discovery, more than a hundred analogues have been synthesised by various research groups in the hope of elucidating its structure–activity relationships (SARs) . The biological activities of these analogues and the different synthetic strategies reported have been comprehensively reviewed .…”

Syntheses of potent teixobactin analogues against methicillin-resistant Staphylococcus aureus (MRSA) through the replacement of l-allo-enduracididine with its isosteres

“…4 Several research groups have substituted this amino acid with commercially available building blocks such as Arginine, 6 7 Lysine 8 or Histidine. 12 The obtained analogues were less active than the natural product. However, the biological activity of teixobactin analogues suggests they are still suitable for further development as potential antibacterials.…”

“…reported that Lys10/Arg10, Ser7 and the NH-group of the N terminal phenylalanine are critical for the biological activity of teixobactin analogues. 12 Replacement of Arg10 or Lys10 by His10, Ser7 by Ala7 and N-Methyl phenylalanine1 by N, N-dimethyl phenylalanine1 leads to less active teixobactin analogues compared to Arg10-teixobactin. During the preparation of this manuscript, a series of teixobactin analogues using convergent Ser/Thr ligation was published by Li et.…”

X-ray crystallographic structure of a teixobactin analogue reveals key interactions of the teixobactin pharmacophore

“…1) and related homologues in which arginine is used as a surrogate for allo -enduracididine. 8–13 Very recently, Singh et al reported NMR-based structures and structure-activity-relationships of Arg 10 -teixobactin and its diastereomers at positions 1, 4, 5, and 8. 14 …”