Simplified lipid II-binding antimicrobial peptides: Design, synthesis and antimicrobial activity of bioconjugates of nisin rings A and B with pore-forming peptides

A Chemical Biology Approach to Understanding Molecular Recognition of Lipid II by Nisin(1–12): Synthesis and NMR Ensemble Analysis of Nisin(1–12) and Analogues

“…Another factor to consider,e specially in the interesto fd evelopingm ore stable antibiotics based on the structureo f nisin, [28][29][30][31] is the effect of residue mutation within lantibiotic binding rings on either solutionc onformation or antibacterial activity.S ignificant efforts have been directed towards understanding the effects of dehydro residue replacement,a st hese residues contribute to the metabolic instability of these pep-tides, however no clear picture has yet emerged. Palmer et al have shown that substitution of Dha5 for Ala in nisin ring A leads to significant conformational change of the isolated ring A, [32] conversely,o ur NMR studies [25] comparingi solated ring A structures of nisina nd mutacin Iw ith saturated analogues of mutacin Ir ing Ai ndicated that the replacement of Dha5 by either Ser or Ala did not significantly affectt he overall conformation of the Leu4-Xaa5-Leu6 portion of ring A.…”

“…Another factor to consider, especially in the interest of developing more stable antibiotics based on the structure of nisin, is the effect of residue mutation within lantibiotic binding rings on either solution conformation or antibacterial activity. Significant efforts have been directed towards understanding the effects of dehydro residue replacement, as these residues contribute to the metabolic instability of these peptides, however no clear picture has yet emerged.…”

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

“…Its modifications often include proteolytic digestion followed by expansion of the fragments by attachment of other constructs such as vancomycin, fragment mimics, lipophilic chains, or pore-forming peptides. [352][353][354][355] Finally, cyclic peptidic scaffolds are also often modified after their isolation from natural or bioengineered sources. Examples include polymyxins or lipodepsipeptide daptomycin, whose 'tail' aa and lipophilic groups were altered, or depsipeptides ramoplanin and telomycin, whose acylation patterns were modified.…”

Ring-opening reactions for the solid-phase synthesis of nisin lipopeptide analogues

“…12 In recent years, truncated nisin conjugates have been investigated by the Tabor, Martin and Cobb groups to mitigate the poor in vivo stability of nisin, caused by degradation at >pH 8. [13][14][15][16] Martin and coworkers recently showed that the first 12 amino acids of nisin, isolated through trypsin-mediated cleavage of the whole peptide, can be connected to a decyl tail which mimics the lipophilic portion of nisin. This semi-synthetic nisin analogue, 1* (Fig.…”