Synthesis and antibacterial studies of teixobactin analogues with non-isostere substitution of enduracididine

Probing key elements of teixobactin–lipid II interactions in membranes

“…Evidence for the critical role of residue 10 backbone comes from amino acid substitutions that alter backbone conformations. For example, proline23 and d -amino acids22,23 at residue 10 result in significant reduction of Txb activity, sometimes even more than side chain substitutions that contain no hydrogen bond donor.…”

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

“…[144] Further comprehensive studies revealed that the synergistic inhibition of both peptidoglycan and teichoic acid synthesis results in cell-wall damage,d elocalization of autolysins,a nd ultimately cell lysis. [149][150][151] This peptide is readily available synthetically and shows excellent antibacterial activity against MRSA (MIC of 0.125 mgmL À1 )a nd 18 additional Gram-positive strains.I mportantly,t he peptide does not exhibit toxicity, neither in vitro nor in vivo (topical administration in arabbit corneal damage model), and clears infections in amouse-eye model of S. aureus keratitis as well as the approved antibiotic moxifloxacin. [146] Va rious groups have pursued the total synthesis of teixobactin and its corresponding analogues.A dditionally, NMR and crystallographic studies have given insight into the structural details of the peptide and identified the macrolactone ring to be essential for pyrophosphate binding and thus the antibiotic effect (all of this is summarized excellently by Guo et al [147] and Fiers et al [148] ).…”

The impact of backbone N‐methylation on the structure‐activity relationship of Leu10‐teixobactin

“…It was found that the minimum inhibitory concentrations (MICs) were comparable with those from previous reports (Table ) including matching MIC values for S . aureus ATCC29213 (0.5 μg/mL) …”