-O-dodecyl tripeptide bromides formed a parallel -sheet structure when they aggregated in water and in CCl 4 . The parallel -sheet was distinguished from the antiparallel counterpart by Fourier transform infrared spectroscopy because the former lacks a weak band at about 1690 cm -1 that is characteristic for the latter. The FT-IR spectra of the aggregate in CCl 4 remained unchanged if the solution was diluted to 0.01 mM, condensed to dryness, or heated to 60°C, and hence, the -sheet was easily formed and thermodynamically stable. The parallel -sheet was also possible to transform into an antiparallel -sheet, for example, by mixing with another tripeptide-containing amphiphile whose tripeptide part had an opposite direction. Transmission electron microscope (TEM) and atomic force microscope (AFM) pictures revealed that the aggregate in CCl 4 is a bundle of small filaments whose diameters are 70-80 Å. Developed interpeptide hydrogen bonding should be formed along the long axis of the filament. The morphological structures and stable peptide arrangements of the present assemblages are similar to those of the amyloid fiber whose accumulation causes fatal diseases.

Oxidative stress appears to be directly involved in the pathogenesis of the neurodegeneration of dopaminergic systems in Parkinson disease. In this study, we formed four dopamine modification adducts derived from docosahexaenoic acid (C22:6/ -3) and arachidonic acid (C18:4/-6), which are known as the major polyunsaturated fatty acids in the brain. Upon incubation of dopamine with fatty acid hydroperoxides and an in vivo experiment using rat brain tissue, all four dopamine adducts were detected. Furthermore, hexanoyl dopamine (HED), an arachidonic acid-derived adduct, caused severe cytotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells, whereas the other adducts were only slightly affected. The HED-induced cell death was found to include apoptosis, which also seems to be mediated by reactive oxygen species generation and mitochondrial abnormality. Additionally, the experiments using monoamine transporter inhibitor and mouse embryonic fibroblast NIH-3T3 cells that lack the monoamine transporter indicate that the HED-induced cytotoxicity might specially occur in the neuronal cells. These data suggest that the formation of the docosahexaenoic acid-and arachidonic acid-derived dopamine adducts in vitro and in vivo, and HED, the arachidonic acid-derived dopamine modification adduct, which caused selective cytotoxicity of neuronal cells, may indicate a novel mechanism responsible for the pathogenesis in Parkinson disease.

In general, an amphiphilic molecule that can form an aggregate in a certain medium, especially an aqueous bilayer aggregate, forms a self-supporting film when the solution is cast onto an appropriate substrate then air dried.[1] The orderly molecular alignment within the cast film is useful for forming an ultrathin layer or coating with few defects. However, the supramolecular cast film has neither mechanical strength nor elasticity. Our aim in the present study is to improve the mechanical strength of the cast film, and to form an elastic supramolecular film that has the elastic properties of a macromolecular film. The prominent advantages of macromolecular films, namely, strength and elasticity, are ascribed to the covalent linkage that constitutes a sequence of the lowest unit molecule, the monomer. Therefore, an alternative interaction is needed to replace the covalent linkage to obtain an elastic supramolecular film. By using multiple H bonding as an alternative, Meijer and co-workers have demonstrated a supramolecular polymer.[2] The monomer of the supramolecular polymer has two sets of H-bonding blocks, for example, pyrimidon, at both edges of the molecule, which links the other molecules by multiple H bonding. The bora-type monomers yield a highly viscous, resinlike liquid. A similar substance has also been reported by Rebek, Jr. and coworkers.[3] Furthermore, the research group of Hutchison demonstrated that the self-assembled monolayer of a glycylglycine-containing amphiphile was stabilized by 3D networks of H bonding.[4] On the other hand, multiple H bonding has been observed as a b-sheet structure in the cast films of the tripeptide-containing amphiphiles.[5] These amphiphiles produce a self-supporting transparent film, but they are extremely brittle. This result means that another interaction that immobilizes the b-sheets will be needed for improving the mechanical strength of the supramolecular film. Thus, we attempted to use the side chains of the peptide part. Because the side chains of the adjacent amino-acid residues locate in opposite directions across the b-sheet plane, [6] the side chains could interlock with counterparts of the other b-sheet planes. This specific interdigitated structure should fasten the b-sheet planes when the peptide part contains at least three consecutive leucine residues as illustrated in Figure 1, which is similar to a zipper or a fastener. To reduce the confusion with the leucine zipper peptides, we prefer to call the aforementioned structure "leucine fastener". The leucine fastener will not be formed if a b-sheet structure is absent. Emphasis is placed on this hierarchy. However, until now, such hierarchic integration has not yet been realized. We demonstrate herein the hierarchic integration of supramolecular monomers, and aim to form a self-supporting elastic film without covalent linkage between the monomers.The supramolecular monomers used in the study are leucine-containing amphiphiles (N + C 11 (Leu) n Glu(OC 12 ) 2 ; n = 2, 3, 4). These amphiphiles dissolve i...

Excessive intake of purine-rich foods elevates serum levels of uric acid. Animal and fish meats contain high amounts of inosine and its related purines, and the reduction of taking those purines is crucial for the improvement of serum uric acid levels. We previously showed that Lactobacillus gasseri PA-3 (PA-3) incorporates adenosine and its related purines and that oral treatment with PA-3 reduced adenosine absorption in rats. This study investigated whether PA-3 also incorporates IMP (inosine 5′-monophosphate), inosine, and hypoxanthine, and whether it reduces their absorption in rats. PA-3 was incubated in vitro with radioisotope (RI)-labeled IMP, inosine, and hypoxanthine, and the incorporation of these compounds by PA-3 was evaluated. In addition, rats were orally administered PA-3 along with RI-labeled inosine 5′-monophosphate, inosine, or hypoxanthine, and the ability of PA-3 to attenuate the absorption of these purines was determined. PA-3 incorporated all three purines and displayed greater proliferation in the presence than in the absence of these purines. Oral administration of PA-3 to rats reduced the absorption of IMP, inosine, and hypoxanthine. These results indicate that PA-3 reduces the absorption of purines contained in foods and it is expected that PA-3 contributes attenuation of the excessive intake of dietary purines.

How does your cluster grow? The nitrogenase P‐cluster [Fe8S7] core has been assembled from the two all‐ferric [Fe4S4] clusters via phosphine desulfurization. This finding suggests that reductive desulfurization from an [Fe4S4] cluster can occur in the maturation process of the P‐cluster of nitrogenase.

N-{4-[4-( l0-Trimethylammoniodecyloxy)phenylazo]benzoyl~-~-alanine alkyl ester bromides with n-C, to -CI3 alkyl chains have been newly synthesized. The bilayer aggregates absorbed at 355 nm when the number of carbons was even and at 320 nm when odd. Regardless of whether the number was even or odd, X-ray diffraction patterns suggested a chain penetration structure, where the tail chains in one molecular layer penetrated into the opposite molecular layer, and hence every other azobenzene group was distributed into the opposite layers. However, a remarkable splitting of the CH, scissoring band into 1473 and 1463 cm-' indicated perpendicular alignments of the trans-zigzag planes of the chains containing an even number of carbons, whereas the singlet CH, scissoring band at 1465 cm-' indicated parallel alignments of the planes of the chains containing an odd number of carbons. In accord with the chain packing, when the amphiphiles possess an even number of carbons, the adjacent neighbouring azobenzenes in each layer were arranged perpendicular to each other. The perpendicular location causes a loss of interchromophore interaction, giving a, , , at 355 nm. In contrast, the azobenzenes in the bilayers of the amphiphiles containing an odd number of carbons were all parallel to each other. Because the molecules were tilted above about 60°, a H aggregate should be predominantly formed, which absorbed at 320 nm. In addition, the amphiphiles containing an even number of carbons formed stronger H bonding than those containing an odd number of carbons.

It is well accepted that frequent and heavy intake of purine-rich foods causes elevation of serum uric acid levels, which is a risk factor of hyperuricemia. Reducing intestinal absorption of dietary purines may attenuate the elevation of serum uric acid levels and exacerbation of hyperuricemia. This reduction may be achieved by the ingestion of lactic acid bacteria that take up purines in the intestine. In this study, we investigated the degree of uptake and utilization of purines of three lactobacilli strains. Among them, Lactobacillus gasseri PA-3 (PA-3) showed the greatest incorporation of C-adenine. PA-3 also incorporatedC-adenosine and C-AMP. Additionally, using defined growth medium, PA-3 demonstrated greater proliferation in the presence of these purines than in their absence. Although further investigation is required, ingestion of PA-3 may lower serum uric acid levels by reducing intestinal absorption of purines in humans.

The all-ferric ½Fe 4 S 4 4þ cluster ½Fe 4 S 4 fNðSiMe 3 Þ 2 g 4 1 and its oneelectron reduced form ½1 − serve as convenient precursors for the synthesis of 3∶1-site differentiated ½Fe 4 S 4 clusters and highpotential iron-sulfur protein (HiPIP) model clusters. The reaction of 1 with four equivalents (equiv) of the bulky thiol HSDmp (Dmp¼ 2,6-ðmesitylÞ 2 C 6 H 3 , mesityl ¼2,4,6-Me 3 C 6 H 2 ) followed by treatment with tetrahydrofuran (THF) resulted in the isolation of ½Fe 4 S 4 ðSDmpÞ 3 ðTHFÞ 3 2. Cluster 2 contains an octahedral iron atom with three THF ligands, and its FeðSÞ 3 ðOÞ 3 coordination environment is relevant to that in the active site of substrate-bound aconitase. An analogous reaction of ½1 − with four equiv of HSDmp gave ½Fe 4 S 4 ðSDmpÞ 4 − 3, which models the oxidized form of HiPIP. The THF ligands in 2 can be replaced by tetramethyl-imidazole (Me 4 Im) to give ½Fe 4 S 4 ðSDmpÞ 3 ðMe 4 ImÞ 4 modeling the ½Fe 4 S 4 ðCysÞ 3 ðHisÞ cluster in hydrogenases, and its one-electron reduced form ½4 − was synthesized from the reaction of 3 with Me 4 Im. The reversible redox couple between 3 and ½3 − was observed at E 1∕2 ¼−820 mV vs. Ag∕Ag þ , and the corresponding reversible couple for 4 and ½4 − is positively shifted by þ440 mV. The cyclic voltammogram of 3 also exhibited a reversible oxidation couple, which indicates generation of the all-ferric ½Fe 4 S 4 4þ cluster, ½Fe 4 S 4 ðSDmpÞ 4 .Fe4S4 cluster | thiolates C uboidal ½Fe 4 S 4 clusters are ubiquitous metal-centers in proteins, expediting electron transfer and enzymatic reactions. These ½Fe 4 S 4 cores are usually bound to four cysteinyl thiolates (Cys) as found in the high-potential iron-sulfur proteins (HiPIP) and widely distributed ferredoxins (Fd). Some ½Fe 4 S 4 clusters carrying an N-or O-donor ligand and three Cys ligands are also known, for example the ½Fe 4 S 4 ðCysÞ 3 ðHisÞ cluster (His ¼ histidinyl imidazole) in [NiFe] and [FeFe] hydrogenases ( Fig. 1) (1-6), and the ½Fe 4 S 4 ðCysÞ 3 ðO-donorÞ cluster in aconitase (7-9) and protochlorophyllide reductase (10). All of these ½Fe 4 S 4 clusters are present in three oxidation states, ½Fe 4 S 4 3þ (HiPIP ox ), ½Fe 4 S 4 2þ (HiPIP red ∕Fd ox ), and ½Fe 4 S 4 þ (Fd red ), while the ½Fe 4 S 4 0 state has been suggested for the cluster in the Fe-protein of nitrogenase (11,12). To date, no ½Fe 4 S 4 4þ cluster has been found in proteins.