Structure and property of self-assemble valinyl bolaform amides having different chirality.

Bolaform amides were designed from N,N'-bis(carboethoxy-L-valinyl)-diaminoethane (1) by linking t-butyloxycarbonyl-valine through ethylenediamine (EDA) to enable spectroscopic and X-ray diffraction analyses. N,N'-Bis(Boc-L-valinyl)-diaminoethane (2) and N,N'-bis(Boc-D-valinyl)-diaminoethane (3) were composed of L-Val and D-Val, respectively. N-(Boc-L-valinyl)-N'-(Boc-D-valinyl)-diaminoethane (4) was composed of both L-Val and D-Val, and was achiral (meso-peptide). Peptide 5 was a 1:1 mixture of 2 and 3, and was also achiral (racemate). These peptides mediated gelation of corn oil at a concentration of approximately 1%. Within crystals, the peptides formed beta-sheet ribbons, but differences were observed in hydrogen-bonding patterns and side-chain arrangements. These differences were also deduced from temperature dependence of amide protons. Force-field calculations based on the crystal structures indicated that association of beta-sheet ribbons had energy benefits, and it was assumed that molecular aggregation progressed spontaneously. These structural studies indicated the chirality of amino acids affected for the properties of bolaform amides.

Effect of asymmetric modification on the conformation of ascidiacyclamide analogs.

Ascidiacyclamide (ASC), cyclo(-Ile1-Oxz2-d-Val3-Thz4-)2 (Oxz=oxazoline and Thz=thiazole) has a C2-symmetric sequence, and the relationships between its conformation and symmetry have been studied. In a previous study, we performed asymmetric modifications in which an Ile residue was replaced by Gly, Leu or Phe to disturb the symmetry [Doi et al. (1999) Biopolymers49, 459-469]. In this study, the modifications were extended. The Ile1 residue was replaced by Gly, Ala, aminoisobutyric acid (Aib), Val, Leu, Phe or d-Ile, and the d-Val3 residue was replaced by Val. The structures of these analogs were analyzed by X-ray diffraction, 1H NMR and CD techniques. X-Ray diffraction analyses revealed that the [Ala1], [Aib1] and [Phe1]ASC analogs are folded, whereas [Val1]ASC has a square form. These structures are the first examples of folded structures for ASC analogs in the crystal state and are similar to the previously reported structures of [Gly1] and [Phe1]ASC in solution. The resonances of amide NH and Thz CH protons linearly shift with temperature changes; in particular, those of [Aib1], [d-Ile1] and [Val3]ASCs exhibited a large temperature dependence. DMSO titration caused nonlinear shifts of proton resonances for all analogs and largely affected [d-Ile1] and [Val3]ASCs. A similar tendency was observed upon the addition of acetone to peptide solutions. Regarding peptide concentration changes, amide NH and Thz CH protons of [Gly1]ASC showed a relatively large dependence. CD spectra of these analogs indicated approximately two patterns in MeCN solution, which were related to the crystal structures. However, all spectra showed a similar positive Cotton effect in TFE solution, except that of [Val3]ASC. In the cytotoxicity test using P388 cells, [Val1]ASC exhibited the strongest activity, whereas the epimers of ASC ([d-Ile1] and [Val3]ASCs), showed fairly moderate activities.

Amphipathic structure of theonellapeptolide-Id, a hydrophobic tridecapeptide lactone from the Okinawa marine sponge Theonella swinhoei.

Theonellapeptolide-Id (TNLP), a cyclic tridecapeptide lactone, was crystallized from dimethylformamide-water solution. In the asymmetric unit, two peptide molecules were combined with solvent molecules, and the total molecular weight was over 3000 Dalton. The crystal structure including solvent molecules was finally determined at 0.80 A resolution using synchrotron radiation. The conformations of two independent molecules were similar to each other and were also similar to the previously reported structure (Doi, Ishida, Kobayashi, Deschamps and Flippen-Anderson, 1999, Acta Crystallogr Sect C, 55, 796-798). About 13 hydrated water molecules were found at disordered 19 sites; they were located at a certain region to avoid contact with aliphatic side-chains of peptolide in the crystal. The spatial disposition of the solvent molecules and peptides subsequently caused the formation of the amphipathic layer.

[Dietary factors and prevention of colon cancer].

Even when the causative factors are known, cancer may still occur in some circumstances. Many mutagenic substances occur in food. The carcinogenic potential of food compounds in humans is not yet clear. If they do play a role in the occurrence of cancer, it would be exceedingly difficult to remove them from the environment. Dietary fiber is generally believed to protect against colorectal cancer. Burkitt first proposed the fiber hypothesis based on his observation of low colon cancer rates in regions of Africa where fiber intake is high. Some case control studies of colorectal cancer have pointed the beneficial effect of total dietary fiber. Dietary fiber consists of plant cell wall polysaccharides and liginin, which are not hydrolyzable by human digestive enzymes, and includes pectin, cellulose, and hemicellulose. Several plausible physical and biochemical mechanisms for the beneficial effect of dietary fiber have been proposed. The risk of colorectal cancer decreases with high intake of total fiber and increased with diets high in animal fat.