Tamaki Kato

Quasi-solid dye sensitised solar cells filled with ionic liquid—increase in efficiencies by specific interaction between conductive polymers and gelators

Photo-energy conversions for quasi-solid dye sensitised solar cells increased when gel electrolytes were combined with conductive polymers as counter electrodes and the conversion surpassed that for DSSCs equipped with conventional Pt counter electrodes.

Additives for Increased Photoenergy Conversion Efficiencies of Quasi-Solid, Dye-Sensitized Solar Cells

Dye-sensitized solar cells (DSCs) are solidified with gelators containing polyvinylpyridine and 1,2,4,5-tetra(bromomethyl)benzene. The photoconversion efficiencies are improved by new additives. Lil and t-butylpyridine are commonly added in electrolytes for increasing short-circuit current (Jsc) and open-circuit voltage (Voc). These additives inhibit our gel electrolyte precursors from solidifying. We found that new additives, combinations of acetic acid, and methylpyrimidine or methylbenzimidazole, do not inhibit the solidification and are effective for increasing both Jsc and Voc. These mechanisms are discussed in terms of electron diffusion coefficients, 13 ion diffusion coefficients, and charge-transfer resistances between counter electrodes and gel electrolytes.

Bicyclic peptides as potent inhibitors of histone deacetylases: optimization of alkyl loop length.

Bicyclic tetrapeptide hydroxamic acids were prepared as histone deacetylase (HDAC) inhibitors, and the evaluated inhibitory activity shows that they are potent against HDAC1 and HDAC4. The in vivo activity depends on alkyl loop length.

Bicyclic tetrapeptides as potent HDAC inhibitors: Effect of aliphatic loop position and hydrophobicity on inhibitory activity

Several histone deacetylase (HDAC) inhibiting bicyclic tetrapeptides have been designed and synthesized through intramolecular ring-closing metathesis (RCM) reaction and peptide cyclization. We designed bicyclic tetrapeptides based on CHAP31, trapoxin B and HC-toxin I. The HDAC inhibitory and p21 promoter assay results showed that the aliphatic loop position as well as the hydrophobicity plays an important role toward the activity of the bicyclic tetrapeptide HDAC inhibitors.

Evaluation of functional groups on amino acids in cyclic tetrapeptides in histone deacetylase inhibition

The naturally occurring cyclic tetrapeptide, chlamydocin, originally isolated from fungus Diheterospora chlamydosphoria, consists of α-aminoisobutyric acid, l-phenylalanine, d-proline and an unusual amino acid (S)-2-amino-8-((S)-oxiran-2-yl)-8-oxooctanoic acid (Aoe) and inhibits the histone deacetylases (HDACs), a class of regulatory enzymes. The epoxyketone moiety of Aoe is the key functional group for inhibition. The cyclic tetrapeptide scaffold is supposed to play important role for effective binding to the surface of enzymes. In place of the epoxyketone group, hydroxamic acid and sulfhydryl group have been applied to design inhibitor ligands to zinc atom in catalytic site of HDACs. In the research for more potent HDAC inhibitors, we replaced the epoxyketone moiety of Aoe with different functional groups and synthesized a series of chlamydocin analogs as HDAC inhibitors. Among the functional groups, methoxymethylketone moiety showed as potent inhibition as the hydroxamic acid. On the contrary, we confirmed that borate, trifruoromethylketone, and 2-aminoanilide are almost inactive in HDAC inhibition.

Purification and identification of an IgE suppressor from strawberry in an in vitro immunization system

We purified and identified an IgE suppressor from the strawberry ‘Toyonoka’, based on the decrease of IgE production in in vitro immunization (IVI). Gel filtration experiment indicated that fractions in a 15–48 kDa range and <10 kDa have an IgE suppressive activity. Furthermore, the fraction in 15–48 kDa was subjected to chromatofocusing and found to have activities at isoelectric points, pI 6.0, 7.0, and 8.0–9.2. We focused on the active fractions of pI 8.0–9.2 and the purified a large amount of strawberry extracts by cation exchange resins in batch. A purified 39 kDa protein showed homology to plant glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in N-terminal amino acid sequence and had GAPDH enzymatic activity. Nucleotide sequence and deduced amino acid sequence of the obtained cDNA clone of the protein matched with the sequence of Fragaria x ananassa GAPDH in the GenBank with >98% identical nucleotides and >99% identical amino acids, respectively. The purified strawberry GAPDH suppressed total IgE production in IVI in a dose-dependent manner. From these results, we identified GAPDH as IgE suppressor in the strawberry. Our study may be applicable to the development of new methods to relieve allergic conditions using GAPDH and the screening of other functional factors for human health.

Design and synthesis of peptide-MCA substrates for a novel assay of histone methyltransferases and their inhibitors.

Histone methyltransferases (HMTs) play an important role in controlling gene expression through site-specific methylation of lysines in core and linker histones within chromatin. As the typical HMTs, G9a and Set7/9 have been intensively studied that G9a is specific to the methylation at H3K9 and H3K27 and represses transcription, while Set7/9 methylates at H3K4. In this report we prepared various peptide-MCAs (4-methylcoumaryl-7-amides) related to histone tail and protein-substrates such as p53 and estrogen receptor-α. The fluorogenic substrates are applied for the assay of HMTs and an inhibitor, for example. The most sensitive and specific MCA-substrates to G9a and Set7/9 are discovered. The peptide-MCAs corresponding to the methylation sequences are promising for screening of HMT inhibitors.

Hemispherical synthesis of dendritic poly(L-lysine) combining sixteen free-base porphyrins and sixteen zinc porphyrins

Dendritic poly(L-lysine) combining sixteen free-base porphyrins and sixteen zinc porphyrins hemispherically at the fifth generation was successfully synthesised and showed intramolecular fluorescence energy transfer in DMF.

Spectroscopic characterization of an assembled pair of free-base and zinc porphyrins linked by the cyclic β-sheet peptide Gramicidin S

A pair of porphyrins was linked to the Orn side chains of Gramicidin S [cyclo(–D-Phe–Pro–Val–Orn–Leu–)2] and its derivatives via the amide bonds; the assorted porphyrins were characterized by various spectroscopic methods. The high-field shifts of the porphyrin signals in the 1H NMR spectrum and the exciton-coupled Cotton effects in the CD spectrum of cyclo[–D-Phe–Pro–Val–Orn(Por)–Leu–]2 are both intense compared to those of cyclo[–D-Phe–Pro–Val–Dab(Por)–Leu–]2 or cyclo[–D-Phe–Pro–Val–Lys(Por)–Leu–]2 (Dab, diaminobutyric acid; Por, the side-chain linked porphyrin). Some 1H NMR signals of the tolyl protons of the porphyrins coalesce at 353 K in CD2Cl2, which reveals dynamic processes of the porphyrins. The intensities of the Cotton effect are: Gramicidin S with a pair of free-base porphyrins ≈ Gramicidin S with a free-base porphyrin and a zinc porphyrin   CH2Cl2 > DMF.

An efficient synthesis of SK-658 and its analogs as potent histone deacetylase inhibitors

SK-658 is a potent histone deacetylase (HDAC) inhibitor that showed higher activity than SAHA due to the presence of extended hydrophobic group. We designed and synthesized thioester and SS-hybrid bearing SK-658 analogs as HDAC inhibitors. All the compounds were active in nano molar range and showed higher inhibitory activity than SAHA and SK-658. Among these, disulfide compounds showed the highest activity.