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1.
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.  相似文献   

2.
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’ 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 μg mL?1 against Staphylococcus aureus and a selectivity (=HC50/MIC90) of 650 was discovered, the most selective SMAMP to date.  相似文献   

3.
The promise of proteomics to provide a vast library of protein structural data is exciting to scientists desiring an unprecedented understanding of the relationship between protein structure and function. This powerful knowledge will provide insight into the design rules for proteomimetics which are oligomers and polymers that can be more stable and inexpensive to produce than natural proteins, but still emulate the main biological function of the natural molecule. This Emerging Area article is intended to stimulate discussion on innovative strategies to design the next generation of proteomimetics. Specifically we will examine the design evolution of facially amphiphilic aryl oligomers, compounds that act as synthetic mimics of antimicrobial peptides (SMAMPs) and are known to interact with lipid bilayers. An increasingly important goal in the field of antimicrobial polymers is to develop strategies to rationally design membrane-binding SMAMPs, that are highly cell-selective, from any preferred backbone and molecular weight. It is expected that lessons learned from studying these oligomers can be applied to other systems where mimics are desired to interact with extended surfaces and where it would be most productive to consider mimicking the protein of interest with a large molecule. Obvious examples include disrupting protein-protein interactions or binding long tracts of DNA to control gene expression.  相似文献   

4.
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.  相似文献   

5.
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.  相似文献   

6.
Facially amphiphilic (FA) phenylene ethynylene (PE) polymers that self-assemble in aqueous solution were studied by small-angle X-ray diffraction (SAXD) and found to self-assemble into bilayers with a fully extended backbone. The resulting bilayers have long-range liquid-crystalline order. This self-assembly is programmed into the molecule by placing polar and nonpolar groups at precise locations so that they segregate onto opposite sides of the molecular structure. The absence of FA patterning generated an amorphous sample confirming the importance of this programmed amphiphilicity in the self-assembly process. Facially amphiphilic patterning represents a new design criterion for supramolecular chemistry, illustrated here in the observation of molecular ordering into bilayers reminiscent of self-assembled structures commonly found in biology, including amphiphilic beta-sheet polypeptides and phospholipid bilayers.  相似文献   

7.
Four families of hyperbranched amphiphilic block copolymers of styrene (Sty, less polar monomer) and 2‐vinylpyridine (2VPy, one of the two more polar monomers) or 4‐vinylpyridine (4VPy, the other polar monomer) were prepared via self‐condensing vinyl reversible addition‐fragmentation chain transfer polymerization (SCVP‐RAFT). Two families contained 4VPy as the more polar monomer, one of which possessing a Sty‐b‐4VPy architecture, and the other possessing the reverse block architecture. The other two families bore 2VPy as the more polar monomer and had either a 2VPy‐b‐Sty or a Sty‐b‐2VPy architecture. Characterization of the hyperbranched block copolymers in terms of their molecular weights and compositions indicated better control when the VPy monomers were polymerized first. Control over the molecular weights of the hyperbranched copolymers was also confirmed with the aminolysis of the dithioester moiety at the branching points to produce linear polymers with number‐average molecular weights slightly greater than the theoretically expected ones, due to recombination of the resulting thiol‐terminated linear polymers. The amphiphilicity of the hyperbranched copolymers led to their self‐assembly in selective solvents, which was probed using atomic force microscopy and dynamic light scattering, which indicated the formation of large spherical micelles of uniform diameter. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1310–1319  相似文献   

8.
The effects of supramolecular equilibrium polymers on surface forces are studied by both a phenomenological Landau type analysis and a molecular model based on a Bethe-Guggenheim approximation. We point out that surface forces brought about by equilibrium polymers may be completely different from what can be found with "ordinary" polymers. The new feature is the role of inversion (a)symmetry or "directionality" of the associating unit molecules ("monomers"). Symmetric B-B monomers (where B denotes a self-complementary binding group) give rise to nondirectional chains and lead to attractive forces between similar surfaces. Asymmetric A-D monomers (where A and D denote complementary acceptor and donor groups, respectively) produce directional chains and can cause strong repulsion. The range of the attractive force has a maximum at intermediate concentration, while the range of the repulsive force increases over the whole concentration range.  相似文献   

9.
Polystyrene (PS) with molecular weight of 2.58?×?104 was grafted to multi-walled carbon nanotubes (MWCNTs) via covalent bonds. The modified tubes can self-assemble as regular bundles in tetrahydrofuran (THF) and benzene while unmodified ones cannot but agglomerate seriously and irregularly in the same solvents. In order to find out the role that polymer plays in self-assembly, a series of PS in different molecular weights were synthesized and grafted on the surface of MWCNTs. THF and benzene are two selective solvents because they are well compatible with PS but bad with tubes. Consequently, grafted MWCNTs show amphiphilicity in them. Solvent-philic/solvent-phobic interaction controls the self-assembly driving force. Small PS offers MWCNTs worse compatibility and poorer amphiphilicity than big PS. With amphiphilicity faded, grafted tubes lose self-assembly ability gradually. Meanwhile, degenerated compatibility cripples tubes’ mobility. Therefore, both number and size of self-assemblies (SAs) decline when molecular weight of grafted PS diminishes. SAs lose their regularity and structural integrativity at the same time. Turbiscan stability index was introduced to quantify the compatibility between dispersate and solvents. Besides, a solvent-philic/solvent-phobic balance system was proposed to calculate compatibility and amphiphilicity of all the modified tubes. This model establishes a connection between compatibility, amphiphilicity, and self-assembly behaviors of modified MWCNTs.  相似文献   

10.
A similarity rule due to Markovitz is used for the correlation of the relaxation modulus for different polymeric materials. This rule has long been employed implicitly in the empirical shifting rules for the reduction to common curves of viscoelastic data measured on the same polymer over a range of temperatures and concentrations. It is shown here for the rubbery regime of polydisperse polymers that when relaxation moduli are scaled with the steady-state compliance and the time with the mean relaxation time, data for a variety of amorphous polymeric materials tend to plot on a common curve. This suggests that the dimensionless rubber modulus is, to first order, a common function of dimensionless time for materials which include whole polymers and polymer solutions, the effects of temperature and concentration being automatically incorporated into the two scaling parameters. For materials with sufficient polydispersity the correlation appears to be valid over a wide range of the available experimental data. These amorphous materials appear to share only one feature, flexible molecules with broadly distributed molecular weights. For narrowly dispersed polymers the modulus in the terminal zone is also correlated according to the above rule, but the influence of other parameters appears as the transition to the glassy regime is approached. An additional application of the similarity rule allows the relaxation modulus computed from molecular dynamics simulations of idealized polymers to be compared with experimental moduli for real materials even though the characteristic times for these systems differ by more than ten orders of magnitude.  相似文献   

11.
12.
Wan F  He W  Zhang J  Ying Q  Chu B 《Electrophoresis》2006,27(19):3712-3723
Linear polyacrylamide (LPA) has been widely used as a replaceable separation matrix in CE. An increase in the molecular weight of the separation medium favors the separation of larger DNA fragments. In order to obtain ultrahigh-molecular-weight (UHMW) LPA, a "frozen" method was developed to synthesize the LPA homopolymer. This approach has three major advantages when compared with other existing routes of LPA synthesis: (i) long LPA chains could be obtained easily, with their average molecular weight (MW) being in the high 10 MDa range; (ii) the desired MW could be adjusted over a broad range by controlling the temperature and the concentration of initiators during synthesis; (iii) the product solution contains only a tiny amount of impurity besides the solvent and LPA. Both static and dynamic laser light scattering measurements were carried out to characterize the synthesized LPA in the buffer solution. The DNA sequencing matrix prepared from LPA using this method was studied and the results were compared with the newly developed commercial product POP7 from Applied Biosystems. It should be noted that this approach can be applied to synthesize other water-soluble polymers, resulting in UHMW products because the chain transfer constant is smaller at lower temperatures.  相似文献   

13.
A series of 12‐amino acid peptide analogs is designed using point mutation strategy based on an α‐helical peptide template. The first mutation in the series, KL12, has an idealized facial amphiphilicity. Subsequent mutations are performed to increase hydrophobic or cationic contents. Idealized facial amphiphilicity show enhanced antimicrobial activity and selectivity against most of the tested microbes. Increasing hydrophobic contents further enhance antimicrobial potency; however, selectivity of the most hydrophobic analog is impaired due to non‐specific interactions with mammalian cell membrane. This study demonstrates that facial amphiphilicity and hydrophobic content are strongly correlated with antimicrobial activity and selectivity of antimicrobial peptides.  相似文献   

14.
Cationic poly(phenylene ethynylene)- (PPE-) based conjugated polyelectrolytes (CPEs) with six different chain lengths ranging in degree of polymerization from ~7 to ~49 were synthesized from organic-soluble precursor polymers. The molecular weight of the precursor polymers was controlled by the amount of a monofunctional "end-capping" agent added to the polymerization reaction. Cationic CPEs were prepared by quaternization of amine groups to tetraalkylammonium groups. Their structure-property relationships were investigated by observing their photophysical properties and antibacterial activity. The polymers were found to exhibit a chain-length dependence in their photophysical properties. It has also been observed that the polymers exhibit effective antibacterial activity against both Gram-positive and Gram-negative bacteria under UV irradiation, whereas they show little antibacterial activity in the dark. An effect of chain length on the light-activated antibacterial activity was also found: The shortest polymer (n=7) exhibited the most effective antibacterial activity against both Gram-positive and Gram-negative bacteria.  相似文献   

15.
This paper describes the use of micropatterned agarose stamps prepared by molding against PDMS masters to print patterns of bacteria on agar plates. Topographically patterned agarose stamps were inked with suspensions of bacteria; these stamps generated patterns of bacteria with features as small as 200 microm over areas as large as 50 cm2. Stamps with many small features (>200 microm) were used to study patterns of bacteria growing on media containing gradients of small molecules; stamps with larger features (>750 microm) were used to print different strains of bacteria simultaneously. The stamp transfers only a small percentage of cells that are on its surface to the agar at a time; it is thus possible to replica-pattern hundreds of times with a single inking. The use of soft stamps provides other useful functions. Stamps are easily customized to provide a range of patterns. When culture media is included in the agarose stamp, cells divide and thrive on the surface. The resulting "living stamp" regenerates its "ink" and can be used to pattern surfaces repetitively for a month. This method is rapid, reproducible, convenient, and can be used to control the pattern, spacing, and orientation between colonies of different bacteria.  相似文献   

16.
A new method for the synthesis of star polymers with high molecular weight and narrow molecular weight distribution (MWD) is presented. The star copolymers were prepared by atom transfer radical (co)polymerization (ATRP) of linear macromonomers with divinyl cross-linkers using low molar mass initiator. In contrast to prior "arm-first" procedures with macroinitiators, by using lower ratio of concentration of initiator to MM, the star polymers contained less initiating sites in the core, which decreased the extent of star-star coupling reactions and resulted in formation of star polymers with narrower MWD. Addition of more cross-linker and initiator during the reaction increased the star molecular weight and star yield while retaining the narrow MWD of the star polymer. For example, we synthesized a star polymer with molecular weight Mn = 466 000 g/mol and Mw/Mn < 1.2 in >98% yield.  相似文献   

17.
Poly(p-phenylene pyromellitamic acid)s were synthesized over the weight-average molecular weight range 8,000 to 22,000. The polymers were recovered as amorphous powders composed of 3–4 × 1–2 μ platelets 0.1–0.2 μ thick containing 20–30% associated solvent. Consumption of reactants and attainment of the ultimate molecular weight of the polymer were found to occur within the first few minutes of reaction. The polymers were characterized by scanning electron microscopy; ultraviolet, visible, near-infrared, and infrared spectroscopy; x-ray analysis; viscometry; and light-scattering photometry. The intrinsic viscosity–molecular weight relation for the polymer in DMF was \documentclass{article}\pagestyle{empty}\begin{document}$ [\eta ] = 25.2 \times 10^{ - 4} \bar M_w^{0.56} $\end{document}.  相似文献   

18.
Measurements of dielectric relaxation have been made for a series of solutions of poly(methyl methacrylate) in toluene. A range of concentrations between 2% and 20% was used for a number of polymers of differing molecular weights. The dispersion was studied over the frequency range 103-106 Hz for temperatures between ?90°C and +20°C. It has been found that both the distribution of relaxation times and the activation energy increase with increasing concentration. The magnitudes of the effects vary with molecular weight. A significant observation is that the increase in dielectric constant with concentration is not linear.  相似文献   

19.
Effects of a common-ion salt, n-Bu4NClO4, on the cationic polymerization of styrene and p-chlorostyrene by acetyl perchlorate were studied in a variety of solvents at 0°C. In polymerization (in CH2Cl2) which yielded polymers with a bimodal molecular weight distribution (MWD), addition of the salt suppressed the formation of higher polymers, but affected neither the molecular weight nor the steric structure of the lower polymers. The polymerization rate decreased with increasing salt concentration and became constant at or above a certain concentration. In nitrobenzene, on the other hand, the MWD of the polymers was unimodal and steric structure was unchanged even in the presence of salt at a concentration 50 times that of the catalyst. However, the polymerization rate and the polymer molecular weight decreased monotonically as salt concentration increased. On the basis of these results, it was concluded that the ion pair in methylene chloride differs from that in nitrobenzene, and that the species in the latter solvent is similar in nature to free ions. The fractional contribution of the dissociated and nondissociated propagating species to polymer formation was determined from the rate depression caused by addition of the salt.  相似文献   

20.
Supramolecular amphiphiles (SA), also named superamphiphiles, refer to amphiphiles that are formed by non-covalent interactions. This tutorial review focuses on the molecular architectures of SAs, including diversified topologies such as single chain, double chain, bolaform, gemini and rotaxane types. Non-covalent syntheses that have been employed to fabricate SAs are driven by hydrogen bonding, electrostatic attraction, host-guest recognition, charge transfer interaction, metal coordination and so on. It should be noted that SAs can be either small organic molecules or polymers. SAs allow for tuning of their amphiphilicity in a reversible fashion, leading to controlled self-assembly and disassembly. This line of research has been enriching traditional colloid chemistry and current supramolecular chemistry, and the application of SAs in the field of functional supramolecular materials is keenly anticipated.  相似文献   

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