Synthesis of Antibacterial Nisin–Peptoid Hybrids Using Click Methodology
Hannah L. Bolt,
Laurens H. J. Kleijn,
Nathaniel I. Martin,
Steven L. Cobb
Affiliations
Hannah L. Bolt
Center for Global Infectious Diseases, Department of Chemistry, Durham University, South Road, Durham DH1 3LE, UK
Laurens H. J. Kleijn
Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
Nathaniel I. Martin
Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
Steven L. Cobb
Center for Global Infectious Diseases, Department of Chemistry, Durham University, South Road, Durham DH1 3LE, UK
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.
