@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 {737,
	title = {Fast disinfecting antimicrobial surfaces.},
	journal = {Langmuir},
	volume = {25},
	year = {2009},
	month = {2009 Jan 20},
	pages = {1060-7},
	abstract = {Silicon wafers and glass surfaces were functionalized with facially amphiphilic antimicrobial copolymers using the "grafting from" technique. Surface-initiated atom transfer radical polymerization (ATRP) was used to grow poly(butylmethacrylate)-co-poly(Boc-aminoethyl methacrylate) from the surfaces. Upon Boc-deprotection, these surfaces became highly antimicrobial and killed S. aureus and E. coli 100\% in less than 5 min. The molecular weight and grafting density of the polymer were controlled by varying the polymerization time and initiator surface density. Antimicrobial studies showed that the killing efficiency of these surfaces was independent of polymer layer thickness or grafting density within the range of surfaces studied.},
	keywords = {Anti-Bacterial Agents, Escherichia coli, Glass, Microbial Sensitivity Tests, Molecular Structure, Particle Size, Polymethacrylic Acids, Silicon, Staphylococcus aureus, Surface Properties},
	issn = {0743-7463},
	doi = {10.1021/la802953v},
	author = {Madkour, Ahmad E and Dabkowski, Jeffery M and Nusslein, Klaus and Tew, Gregory N}
}
@article {738,
	title = {Hydrophilic modifications of an amphiphilic polynorbornene and the effects on its hemolytic and antibacterial activity.},
	journal = {Biomacromolecules},
	volume = {10},
	year = {2009},
	month = {2009 Feb 9},
	pages = {353-9},
	abstract = {Here we report the modification of an amphiphilic antibacterial polynorbornene, Poly3, via incorporation of hydrophilic, biocompatible groups. The sugar, zwitterionic, and polyethylene glycol based moieties were incorporated in varying ratios by copolymerization and postpolymerization techniques. Well-defined copolymers with molecular weights of 3 kDa and narrow polydispersity indices ranging from 1.08 to 1.15 were obtained. The effects of these modifications on the biological activity of these polymers were analyzed by determining their minimum inhibitory concentrations (MIC) and their hemolytic activities (HC50).},
	keywords = {Anti-Bacterial Agents, Bacteria, Biocompatible Materials, Carbohydrates, Hemolysis, Microbial Sensitivity Tests, Plastics, Polyethylene, Static Electricity},
	issn = {1526-4602},
	doi = {10.1021/bm801129y},
	author = {Colak, Semra 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 {747,
	title = {Broad-spectrum antibacterial activity by a novel abiogenic peptide mimic.},
	journal = {Microbiology},
	volume = {152},
	year = {2006},
	month = {2006 Jul},
	pages = {1913-8},
	abstract = {The human-mediated use and abuse of classical antibiotics has created a strong selective pressure for the rapid evolution of antibiotic resistance. As resistance levels rise, and the efficacy of classical antibiotics wanes, the intensity of the search for alternative antimicrobials has increased. One class of molecules that has attracted much attention is the antimicrobial peptides (AMPs). They exhibit broad-spectrum activity, they are potent and they are widespread as part of the innate defence system of both vertebrates and invertebrates. However, peptides are complex molecules that suffer from proteolytic degradation. The ability to capture the essential properties of antimicrobial peptides in simple easy-to-prepare molecules that are abiotic in origin and non-proteolytic offers many advantages. Mechanistic and structural knowledge of existing AMPs was used to design a novel compound that mimics the biochemical activity of an AMP. This report describes the development and in vitro characterization of a small peptide mimic that exhibited quick-acting and selective antibacterial activity against a broad range of bacteria, including numerous clinically relevant strains, at low MIC values.},
	keywords = {Anti-Bacterial Agents, Drug Design, Humans, Microbial Sensitivity Tests, Peptides},
	issn = {1350-0872},
	doi = {10.1099/mic.0.28812-0},
	author = {N{\"u}sslein, Klaus and Arnt, Lachelle and Rennie, Jason and Owens, Cullen and Tew, Gregory N}
}
@article {750,
	title = {Simple oligomers as antimicrobial peptide mimics.},
	journal = {J Ind Microbiol Biotechnol},
	volume = {32},
	year = {2005},
	month = {2005 Jul},
	pages = {296-300},
	abstract = {New approaches to antibiotic design are desperately needed. The design of simple oligomers that capture the shape and biological function of natural antimicrobial peptides could prove to be versatile and highly successful. We discuss the use of aromatic backbones to design facially amphiphilic (FA) beta-sheet like structures which are potently antimicrobial. These oligomers capture the physiochemical properties of peptides like the Magainins and Defensins, which fold into specific conformations that are amphiphilic resulting in antimicrobial activity. However, natural peptides are expensive to prepare and difficult to produce on large scale. The design of polymers and oligomers that mimic the complex structures and remarkable biological properties of proteins is an important endeavor and provides attractive alternatives to the difficult synthesis of natural peptides. We therefore have designed a series of FA oligomers that are easy to prepare from inexpensive monomers. They adopt structures very reminiscent of amphiphilic beta-sheets and have significant activity with minimal inhibitory concentrations at 6 h in the low microgram per ml range (muM to nM). They are active against a broad spectrum of bacteria including gram-positive and gram-negative as well as antibiotic resistant strains.},
	keywords = {Amides, Anti-Bacterial Agents, Antimicrobial Cationic Peptides, Drug Resistance, Bacterial, Gram-Negative Bacteria, Gram-Positive Bacteria, Inhibitory Concentration 50, Peptides, Protein Conformation},
	issn = {1367-5435},
	doi = {10.1007/s10295-005-0219-0},
	author = {Rennie, Jason and Arnt, Lachelle and Tang, Haizhong 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}
}
