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Sum frequency generation (SFG) vibrational spectroscopy is employed to study the molecular interactions between a single substrate supported lipid bilayer and an amphiphilic antibiotic compound with a designed based on the common structural motif of natural antimicrobial peptides. The interfacial sensitivity of SFG allows real-time in situ monitoring of ordering changes in both leaflets of the bilayer and orientation of the compound simultaneously.

Several studies are conducted to explain the formation and properties of the bifunctional layer-by-layer (LbL) construct made by the combination of permanent microbicidal polyelectrolyte multilayered (PEM) base film with a hydrolytically degradable PEM top film. These films are shown to be extremely efficient and hence can be used as coatings for different implantable devices.

[Super 31]P and [super 19]F solid-state NMR spectroscopy are applied to study the the lipid interaction, depth of insertion, orientation, and dynamics of an arylamide, PMX30016 and gain better insight into the mechanism of action of the antimicrobial arylamide foldamers. The results suggested that antimicrobial arylamides destabilize anionic lipid membranes primarily by altering the membrane electric potential profile, and the spinning molecular knife might additionally create transient defects in the lipid membrane.

Extensive 2D NMR and MS techniques were used for structural characterization of eight new antimicrobial natural products named chrysophaentins A-H belonging to a new structural class isolated from the marine chrysophyte alga Chrysophaeum taylori. Chrysophaentin A, identified as one of the most potent antibiotic, inhibited the growth of clinically relevant gram-positive bacteria including methicillin-resistant Staphylococcus aureus, multidrug-resistant S. aureus and vancomycin-resistant Enterococcus faecium.

[Super 19]F NMR solid-state analysis was performed to isolate native membranes from erythrocyte ghosts and bacterial protoplasts and prepare them as macroscopically oriented samples. The characteristic fingerprint splitting of the membrane-bound antimicrobial peptide PGLa detected by [super 19]F reporter group indicated that the peptide helix binds to the native membranes in a surface alignment, although with a higher affinity in the prokaryotic than the eukaryotic system.

A paramagnetic copper-chelated lipid is used to enhance the spin-lattice relaxation and thereby speed up solid-state NMR measurements. The results have shown a 6.2-fold speed increase and a 2.7-fold improvement in signal-to-noise ratio for solid-state NMR experiments under magic-angle spinning and static conditions.

The article presents a new approach, which employs a modified nonwoven fabric as a thin film detection/response system for the pathogenic bacteria. The systems are shown to be widely used as responsive dressings with the release of antimicrobials.

The role of the leader peptide of McjA is examined and is shown that only the eight C-terminal amino acids of this leader peptide are needed for maturation of the antimicrobial peptide microcin J25 (MccJ25). Alanine scanning mutagenesis studies have shown that the Thr-35 residue in the leader peptide is vital for correct processing of McjA into mature MccJ25, whereas the charged amino acids have not played a major role in the maturation of MccJ25.

A new method is described for obtaining information about the conformational dynamics of membrane-proteins by using solid-state NMR experiments of oriented samples. The method is shown for the antimicrobial peptaibol alamethicin for which combined analysis of anisotropic interactions for the [Aib.sub.8] residue has given information about helix-tilt angle, wobbling and oscillatory rotation around the helix axis in the membrane bound state.

The secondary metabolites platensimycin and platencin, isolated from the bacterial strain Streptomyces platensis, have represented a novel class of natural products displaying potent antimicrobial activity. The syntheses of platecin have shown the power of the cobalt-catalyzed asymmetric Diels-Alder reaction and the one-pot reductive rearrangement of [3.2.1] bicyclic ketones to [2.2.2] bicyclic olefins.

One member of a prototypical class of antimicrobial oligomers is used for studying pore formation in cardiolipin-rich membranes and both vesicle dye-leakage assays and small-angle X-ray scattering are used for studying bilayer remodeling. The results have shown that the presence of negative intrinsic curvature lipids is necessary for pore formation by this class of molecules.

The biological activity of the selected peptides from the combinatorial library in bacteria, fungi and mammalian cells is studied to characterize the selected peptides and to compare the activity of antimicrobial peptides (AMPs) in vitro and in vivo. The analysis has shown that the methods focusing on screening peptide libraries in vitro for membranes with the appropriate interfacial activity has enabled the design, selection and discovery of novel, potent and broad-spectrum membrane-active antibiotics.

A novel strategy is developed for the total synthesis of sceptrin from the initial failure of an allyl urocanate dimerization route to a successful oxaquadricyclane fragmentation strategy. The exploration of 2-aminoimidazole heterocycle has led to the total synthesis of oxysceptrin and nakamuric acid and a successful construction of the carbon skeleton of axinellamine.

Polymers based on m-phenylene ethylenes (mPE) were designed and synthesized to mimic the amphiphilic, cationic, and rigid structure of antimicrobial peptides (AMPs) and were found to be good mimics of AMPs in terms of their high potency toward microbes and low hemolytic activities. Two mPEs were found to readily insert into anionic model bacterial membranes but to differ in the degree of selectivity between bacterial and mammalian erythrocyte model membranes, demonstrating that mPEs can mimic AMPs' membrane disordering.

The steps taken toward the development of nontoxic antimicrobial synthetic polymers to determine the structure-activity relationship of amphiphilic polymethacrylate derivatives as measured via antimicrobial and hemolytic activities are described. This class of synthetic polymers is inexpensive and easy to prepare, allowing the production of antimicrobial materials on industrial scales.

A solid-state NMR (ssNMR) was employed to study the structure and topology of isotopically labeled piscidins in the membrane-bound state. The results from the NMR restraints established that the piscidins were alpha-helical and oriented parallel to the bilayer surface and topology observed indicates that partitioning of amphipathic, cationic, antimicrobial peptides at the water-bilayer interface allows for favorable peptide-lipid interactions and it might be related to the mechanism of action of piscidins.