Abstract
Antimicrobial peptides and structurally related peptoids offer potential for the development of new antibiotics. However, progress has been hindered by challenges presented by poor in vivo stability (peptides) or lack of selectivity (peptoids). Herein, we have developed a process to prepare novel hybrid antibacterial agents that combine both linear peptoids (increased in vivo stability compared to peptides) and a nisin fragment (lipid II targeting domain). The hybrid nisin–peptoids prepared were shown to have low micromolar activity (comparable to natural nisin) against methicillin-resistant Staphylococcus aureus.
Highlights
The rapid emergence of antibiotic resistance against commonly used frontline treatments poses a serious threat to global health and has emphasized the need for novel antimicrobials to be developed.This urgency is highlighted by increasing academic and industrial interest in the field and the establishment of enterprises such as the 2015 Ross Fund and the 10 × ‘20 Initiative both of which encourage the delivery of new antimicrobial drug classes [1,2].Nisin is a polycyclic peptide produced by several strains of the Gram-positive bacteriumLactococcus lactis and is an antimicrobial with nanomolar activity against other Gram-positive bacteria [3,4]
In particular the A/B ring system at nisin’s N-terminus has been shown to bind to lipid II, which is a crucial membrane component used in bacterial cell wall synthesis
Following lipid II binding, nisin can insert into the bacterial plasma membrane and create pores that cause cell leakage leading to cell death [5,7,8,9,10,11,12]
Summary
The rapid emergence of antibiotic resistance against commonly used frontline treatments poses a serious threat to global health and has emphasized the need for novel antimicrobials to be developed.This urgency is highlighted by increasing academic and industrial interest in the field and the establishment of enterprises such as the 2015 Ross Fund and the 10 × ‘20 Initiative both of which encourage the delivery of new antimicrobial drug classes [1,2].Nisin is a polycyclic peptide produced by several strains of the Gram-positive bacteriumLactococcus lactis and is an antimicrobial with nanomolar activity against other Gram-positive bacteria [3,4]. The rapid emergence of antibiotic resistance against commonly used frontline treatments poses a serious threat to global health and has emphasized the need for novel antimicrobials to be developed. This urgency is highlighted by increasing academic and industrial interest in the field and the establishment of enterprises such as the 2015 Ross Fund and the 10 × ‘20 Initiative both of which encourage the delivery of new antimicrobial drug classes [1,2]. Following lipid II binding, nisin can insert into the bacterial plasma membrane and create pores that cause cell leakage leading to cell death [5,7,8,9,10,11,12]
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