Antimicrobial polymers prepared by ROMP with unprecedented selectivity: a molecular construction kit approach.

TitleAntimicrobial polymers prepared by ROMP with unprecedented selectivity: a molecular construction kit approach.
Publication TypeJournal Article
Year of Publication2008
AuthorsLienkamp K, Madkour AE, Musante A, Nelson CF, Nüsslein K, Tew GN
JournalJ Am Chem Soc
Volume130
Issue30
Pagination9836-43
Date Published2008 Jul 30
ISSN1520-5126
KeywordsAnti-Infective Agents, Antimicrobial Cationic Peptides, Biomimetic Materials, Erythrocytes, Escherichia coli, Hemolysis, Humans, Hydrophobic and Hydrophilic Interactions, Microbial Sensitivity Tests, Molecular Weight, Norbornanes, Polymers, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Staphylococcus aureus, Structure-Activity Relationship
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.

DOI10.1021/ja801662y
Alternate JournalJ. Am. Chem. Soc.
PubMed ID18593128