Antimicrobial Polymers Prepared by ROMP with Unprecedented Selectivity: A Molecular Construction Kit Approach

TLDR

Synthetic mimics of antimicrobial peptides (SMAMPs) replicate natural host‑defence peptides, a key component of the immune system. The study introduces a modular construction kit enabling facile synthesis of diverse facially amphiphilic oxanorbornene‑derived monomers for SMAMP development. Using ring‑opening metathesis polymerization and subsequent deprotection, the kit generates multiple SMAMP series from these monomers. Polymers produced exhibit a 533‑fold increase in bacterial over mammalian cell selectivity, with some 50‑fold preference for Gram‑positive over Gram‑negative bacteria and others the reverse, a double‑selectivity phenomenon unprecedented in polymer systems and attributed to the monomers’ facial amphiphilicity.

Abstract

Synthetic Mimics of Antimicrobial Peptides (SMAMPs) imitate natural host-defense peptides, a vital component of the body’s immune system. This work presents a molecular construction kit that allows the easy and versatile synthesis of a broad variety of facially amphiphilic oxanorbornene-derived monomers. Their ring-opening metathesis polymerization (ROMP) and deprotection provide several series of SMAMPs. Using amphiphilicity, monomer feed ratio, and molecular weight as parameters, polymers with 533 times higher selectivitiy (selecitviy = hemolytic concentration/minimum inhibitory concentration) for bacteria over mammalian cells were discovered. Some of these polymers were 50 times more selective for Gram-positive over Gram-negative bacteria while other polymers surprisingly showed the opposite preference. This kind of “double selectivity” (bacteria over mammalian and one bacterial type over another) is unprecedented in other polymer systems and is attributed to the monomer’s facial amphiphilicity.