@article {733,
	title = {Antimicrobial polymers prepared by ring-opening metathesis polymerization: manipulating antimicrobial properties by organic counterion and charge density variation.},
	journal = {Chemistry},
	volume = {15},
	year = {2009},
	month = {2009 Nov 2},
	pages = {11715-22},
	abstract = {The synthesis and characterization of a series of poly(oxanorbornene)-based synthetic mimics of antimicrobial peptides (SMAMPs) is presented. In the first part, the effect of different organic counterions on the antimicrobial properties of the SMAMPs was investigated. Unexpectedly, adding hydrophobicity by complete anion exchange did not increase the SMAMPs{\textquoteright} antimicrobial activity. It was found by dye-leakage studies that this was due to the loss of membrane activity of these polymers caused by the formation of tight ion pairs between the organic counterions and the polymer backbone. In the second part, the effect of molecular charge density on the biological properties of a SMAMP was investigated. The results suggest that, above a certain charge threshold, neither minimum inhibitory concentration (MIC90) nor hemolytic activity (HC50) is greatly affected by adding more cationic groups to the molecule. A SMAMP with an MIC90 of 4 microg mL(-1) against Staphylococcus aureus and a selectivity (=HC50/MIC90) of 650 was discovered, the most selective SMAMP to date.},
	keywords = {Anti-Infective Agents, Biomimetic Materials, Cations, Diamines, Hemolysis, Hydrophobic and Hydrophilic Interactions, Microbial Sensitivity Tests, Polymers},
	issn = {1521-3765},
	doi = {10.1002/chem.200900606},
	author = {Lienkamp, Karen and Madkour, Ahmad E and Kumar, Kushi-Nidhi and N{\"u}sslein, Klaus and Tew, Gregory N}
}
@article {739,
	title = {Comparison of facially amphiphilic versus segregated monomers in the design of antibacterial copolymers.},
	journal = {Chemistry},
	volume = {15},
	year = {2009},
	month = {2009},
	pages = {433-9},
	abstract = {A direct comparison of two strategies for designing antimicrobial polymers is presented. Previously, we published several reports on the use of facially amphiphilic (FA) monomers which led to polynorbornenes with excellent antimicrobial activities and selectivities. Our polymers obtained by copolymerization of structurally similar segregated monomers, in which cationic and non-polar moieties reside on separate repeat units, led to polymers with less pronounced activities. A wide range of polymer amphiphilicities was surveyed by pairing a cationic oxanorbornene with eleven different non-polar monomers and varying the comonomer feed ratios. Their properties were tested using antimicrobial assays and copolymers possessing intermediate hydrophobicities were the most active. Polymer-induced leakage of dye-filled liposomes and microscopy of polymer-treated bacteria support a membrane-based mode of action. From these results there appears to be profound differences in how a polymer made from FA monomers interacts with the phospholipid bilayer compared with copolymers from segregated monomers. We conclude that a well-defined spatial relationship of the whole polymer is crucial to obtain synthetic mimics of antimicrobial peptides (SMAMPs): charged and non-polar moieties need to be balanced locally, for example, at the monomer level, and not just globally. We advocate the use of FA monomers for better control of biological properties. It is expected that this principle will be usefully applied to other backbones such as the polyacrylates, polystyrenes, and non-natural polyamides.},
	keywords = {Anti-Bacterial Agents, Bacteria, Cell Membrane, Drug Design, Hemolysis, Plastics, Polymers, Surface-Active Agents},
	issn = {1521-3765},
	doi = {10.1002/chem.200801233},
	author = {Gabriel, Gregory J and Maegerlein, Janet A and Nelson, Christopher F and Dabkowski, Jeffrey M and Eren, Tarik and N{\"u}sslein, Klaus and Tew, Gregory N}
}
@article {734,
	title = {"Doubly selective" antimicrobial polymers: how do they differentiate between bacteria?},
	journal = {Chemistry},
	volume = {15},
	year = {2009},
	month = {2009 Nov 2},
	pages = {11710-4},
	abstract = {We have investigated how doubly selective synthetic mimics of antimicrobial peptides (SMAMPs), which can differentiate not only between bacteria and mammalian cells, but also between Gram-negative and Gram-positive bacteria, make the latter distinction. By dye-leakage experiments on model vesicles and complementary experiments on bacteria, we were able to relate the Gram selectivity to structural differences of these bacteria types. We showed that the double membrane of E. coli rather than the difference in lipid composition between E. coli and S. aureus was responsible for Gram selectivity. The molecular-weight-dependent antimicrobial activity of the SMAMPs was shown to be a sieving effect: while the 3000 g mol(-1) SMAMP was able to penetrate the peptidoglycan layer of the Gram-positive S. aureus bacteria, the 50000 g mol(-1) SMAMP got stuck and consequently did not have antimicrobial activity.},
	keywords = {Anti-Infective Agents, Biomimetic Materials, Escherichia coli, Microbial Sensitivity Tests, Peptidoglycan, Polymers, Staphylococcus aureus},
	issn = {1521-3765},
	doi = {10.1002/chem.200802558},
	author = {Lienkamp, Karen and Kumar, Kushi-Nidhi and Som, Abhigyan and N{\"u}sslein, Klaus and Tew, Gregory N}
}
@article {742,
	title = {Antimicrobial polymers prepared by ROMP with unprecedented selectivity: a molecular construction kit approach.},
	journal = {J Am Chem Soc},
	volume = {130},
	year = {2008},
	month = {2008 Jul 30},
	pages = {9836-43},
	abstract = {Synthetic Mimics of Antimicrobial Peptides (SMAMPs) imitate natural host-defense peptides, a vital component of the body{\textquoteright}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{\textquoteright}s facial amphiphilicity.},
	keywords = {Anti-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},
	issn = {1520-5126},
	doi = {10.1021/ja801662y},
	author = {Lienkamp, Karen and Madkour, Ahmad E and Musante, Ashlan and Nelson, Christopher F and N{\"u}sslein, Klaus and Tew, Gregory N}
}
@article {741,
	title = {Investigating the effect of increasing charge density on the hemolytic activity of synthetic antimicrobial polymers.},
	journal = {Biomacromolecules},
	volume = {9},
	year = {2008},
	month = {2008 Oct},
	pages = {2805-10},
	abstract = {The current study is aimed at investigating the effect of fine-tuning the cationic character of synthetic mimics of antimicrobial peptides (SMAMPs) on the hemolytic and antibacterial activities. A series of novel norbornene monomers that carry one, two, or three Boc-protected amine functionalities was prepared. Ring-opening metathesis polymerization (ROMP) of the monomers, followed by deprotection of the amine groups resulted in cationic antimicrobial polynorbornenes that carry one, two, and three charges per monomer repeat unit. Increasing the number of amine groups on the most hydrophobic polymer reduced its hemolytic activity significantly. To understand the membrane activity of these polymers, we conducted dye leakage experiments on lipid vesicles that mimic bacteria and red blood cell membranes, and these results showed a strong correlation with the hemolysis data.},
	keywords = {Amines, Anti-Infective Agents, Antimicrobial Cationic Peptides, Chemistry, Pharmaceutical, Drug Design, Erythrocytes, Escherichia coli, Hemolysis, Humans, Lipids, Magnetic Resonance Spectroscopy, Models, Chemical, Peptides, Polymers, Staphylococcus aureus},
	issn = {1526-4602},
	doi = {10.1021/bm800569x},
	author = {Al-Badri, Zoha M and Som, Abhigyan and Lyon, Sarah and Nelson, Christopher F and N{\"u}sslein, Klaus and Tew, Gregory N}
}
@article {740,
	title = {Synthetic mimic of antimicrobial peptide with nonmembrane-disrupting antibacterial properties.},
	journal = {Biomacromolecules},
	volume = {9},
	year = {2008},
	month = {2008 Nov},
	pages = {2980-3},
	abstract = {Polyguanidinium oxanorbornene ( PGON) was synthesized from norbornene monomers via ring-opening metathesis polymerization. This polymer was observed to be strongly antibacterial against Gram-negative and Gram-positive bacteria as well as nonhemolytic against human red blood cells. Time-kill studies indicated that this polymer is lethal and not just bacteriostatic. In sharp contrast to previously reported SMAMPs (synthetic mimics of antimicrobial peptides), PGON did not disrupt membranes in vesicle-dye leakage assays and microscopy experiments. The unique biological properties of PGON, in same ways similar to cell-penetrating peptides, strongly encourage the examination of other novel guanidino containing macromolecules as powerful and selective antimicrobial agents.},
	keywords = {Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Erythrocytes, Gram-Negative Bacteria, Gram-Positive Bacteria, Guanidines, Humans, Microbial Sensitivity Tests, Molecular Mimicry, Polymers},
	issn = {1526-4602},
	doi = {10.1021/bm800855t},
	author = {Gabriel, Gregory J and Madkour, Ahmad E and Dabkowski, Jeffrey M and Nelson, Christopher F and N{\"u}sslein, Klaus and Tew, Gregory N}
}
@article {752,
	title = {Tuning the hemolytic and antibacterial activities of amphiphilic polynorbornene derivatives.},
	journal = {J Am Chem Soc},
	volume = {126},
	year = {2004},
	month = {2004 Dec 8},
	pages = {15870-5},
	abstract = {Amphiphilic cationic polynorbornene derivatives, soluble in water, were prepared from modular norbornene monomers, with a wide range of molecular weights (M(n) = 1600-137 500 g/mol) and narrow polydispersities (PDI = 1.1-1.3). The antibacterial activity determined by growth inhibition assays and the hemolytic activity against human red blood cells were measured and compared to determine the selectivity of the polymers for bacterial over mammalian cells. The effects of monomer repeat unit hydrophobicity and polymer molecular weight on antibacterial and hemolytic activities were determined. The hydrophobicity of the repeat unit was observed to have dramatic effects on antibacterial and hemolytic activities. Lipid membrane disruption activities of the polymers was confirmed by measuring polymer-induced dye leakage from large unilamellar vesicles. By tuning the overall hydrophobicity of the polymer through random copolymerizations of modular norbornene derivatives, highly selective, nonhemolytic antibacterial activities were obtained. For appropriate monomer composition, selectivity against bacteria versus human red blood cells was determined to be over 100.},
	keywords = {Anti-Bacterial Agents, Bacillus subtilis, Cell Membrane, Cholesterol, Erythrocytes, Escherichia coli, Hemolysis, Humans, Liposomes, Microbial Sensitivity Tests, Molecular Weight, Norbornanes, Polymers, Structure-Activity Relationship},
	issn = {0002-7863},
	doi = {10.1021/ja045664d},
	author = {Ilker, M Firat and N{\"u}sslein, Klaus and Tew, Gregory N and Coughlin, E Bryan}
}
