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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.

The hyperthermophilic archaeon Pyrococcus furiosus was used to demonstrate the role of nitric oxide in Roussin's black salt (RBS) toxicity and the mechanism which involves membrane disruption leading to cell lysis. The results proposed RBS to be a new class of inorganic antimicrobial agent that also have potential use as an inert cell-lysing agent.

A detailed characterization of peptide-membrane interactions of dermaseptin (Drs B2), which is a 33-residue-long cationic, [alpha]-helical antimicrobial peptide endowed with membrane-damaging activity against a wide range of microorganisms such as bacteria, yeast, fungi, and protozoa is described. The results showed that Drs B2 could adopt a flexible helix-hinge-helix structure in a membrane environment with a strong positive curvature strain that permits the concomitant insertion of the strongly hydrophobic N- and C-termini of the peptide into the acyl core of the membrane.

The development of a concise route for the preparation of new tetra-orthogonally protected (2S,6R)-lanthionines is described. The new orthogonally protected lanthionines could be used to study the lantibiotic family of antimicrobial peptides.

The combined lactic acid, monolaurin, and nisin effects on time-to-detection extension are greater than any single or paired combination effect that demonstrates a synergistic interaction among the antimicrobials. The results showed that lactic acid-enhanced monolaurin C12:0 absorption into the cell membrane increased membrane fluidity resulting in increased nisin activity.

A biosynthetic study on spiro-mamakone A, a potently cytotoxic and antimicrobial compound from an endophytic fungus isolated from the New Zealand native tree Knightia excelsa is reported. The biosynthesis proceeds via an unprecedented symmetric enedione with the two halves of the molecule formed from two separate pentaketide units connected by oxidative coupling and have confirmed the origin of polyketide to the spirobisnaphthalene class of compounds.

A method is described for converting tert-butyl benzoates or tert-butyl 1-naphthoates into derivatives having an alkyl or substituted alkyl group. The method can be applied to the synthesis of the antimicrobial fungal metabolite culpin.

A method based on selected amino acid alterations in the peptide template was used to identify novel C3a peptide variants with enhanced antimicrobial effects. The results provide insights into the structure-activity relationships associated with the function and specificity of antimicrobial C3a and related analogues and also into the forces that drive evolution of antimicrobial peptides.

The studies and synthesis of cateslytin, a positively charged (5+) arginine-rich antimicrobial peptide that mimic bacterial or mammalian systems is presented. The results shed light onto the mode of action of cateslytin on systems modeling mammalian and bacterial membranes.

A series of guidelines useful for the future design of short cationic antimicrobial peptides with high resilience against tryptic degradation are presented. The guidelines can also be applied to generate stabilization of other small cationic peptides against tryptic degradation.

Nuclear magnetic resonance (NMR) study was conducted to study and compare the dynamics and depth of insertion of two tachyplesin-I (TP-I) linear analogs, TPF4 and TPA4, in lipid bilayers. The active TP-I and TPF4 were found to exhibit large-amplitude motions on the NMR timescales, while the inactive TPA4 was immobilized.

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.

Potassium lactate and sodium diacetate was combined with pasteurizing doses of irradiation to control Listeria monocytogenes on frankfurters. The combination was effective to control the growth of monocytogenes on the surface of the frankfurters and it also enhanced the safety of the refrigerated products.

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.

Rational designing of antimicrobial peptides is described using indolicidin analogue CP-11 peptide with the sequence of ILKKWPWWPWRRK-NH(sub)2 and its cyclic disulfide-bonded version cyclo-CP-11 bearing the sequence ICLKKWPWWPWRRCK-NH(sub)2. Results reveal that the cyclo peptide exhibits higher resistance to trypsin which may be due to compact packing of lysine and tryptophan side chains.

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.