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An enantioselective Strecker-type reaction of aldimines and ketimines was developed by using a chiral dilithium(I) binaphthyldisulfonate as a chiral acid–base cooperative catalyst. The present cata...

The ten-eleven translocation (TET) protein family, consisting of three isoforms (TET1/2/3), have been found in mammalian cells and have a crucial role in 5-methylcytosine demethylation in genomic DNA through the catalysis of oxidation reactions assisted by 2-oxoglutarate (2OG). DNA methylation/demethylation contributes to the regulation of gene expression at the transcriptional level, and recent studies have revealed that TET1 is highly elevated in malignant cells of various diseases and related to malignant alteration. TET1 inhibitors based on a scaffold of thioether macrocyclic peptides, which have been discovered by the random nonstandard peptide integrated discovery (RaPID) system, are reported. The affinity-based selection was performed against the TET1 compact catalytic domain (TET1CCD) to yield thioether macrocyclic peptides. These peptides exhibited inhibitory activity of the TET1 catalytic domain (TET1CD), with an IC50 value as low as 1.1 μm. One of the peptides, TiP1, was also able to inhibit TET1CD over TET2CD with tenfold selectivity, although it was likely to target the 2OG binding site; this provides a good starting point to develop more selective inhibitors.

The high-temperature thermolysis of fatty acid–iron complexes generates magnetic nanoparticles (MNPs) of a precisely controlled size coated with fatty acids and dispersed in oil. Because they are water-immiscible, MNPs are unsuitable for water-based biomedical applications. Ligand exchange reactions that transform oil- into water-dispersed MNPs have attracted considerable attention, but are difficult to perform. In this paper, we report the successful preparation of size-controlled and highly water-dispersed MNPs, which have 4, 8 and 20 nm diameter by a unique two-step ligand exchange reaction. As temporary ligands, we selected thiomalic acid (TMA), which possesses moderate affinity toward MNPs and is soluble in both oil and water to remove fatty acids by XANES analyses. Next we selected the citric acids as secondary ligands for TMA-exchanged MNPs to be highly dispersed in water to remove TMA from the surface of MNPs. And the resulting highly water-dispersed MNPs are expected to be available as MRI contrast agents and hyperthermia carriers.

In this study, FG beads (ferrite nanoparticles in the core covered with poly-(styrene-co-glycidyl methacrylate)) were made into fluorescent magnetic carriers (FMCs) containing the fluorescent substance, europium ion (Eu3+) complex. The developed FMCs showed several notable features such as high fluorescence intensity and high dispersibility in water. More importantly, FMCs did not leak Eu3+ complex. It is expected that the FMCs will be a useful tool for biomolecular recognition and imaging and contribute to advancement of a wide range of research fields, including cell biology and molecular imaging.

For affinity purification of drug target protein we have developed magnetic carriers, narrow in size distribution (184±9 nm), which exhibit minimal non-specific binding of unwanted proteins. The carriers were highly dispersed in aqueous solutions and highly resistant to organic solvents, which enabled immobilization of various hydrophobic chemicals as probes on the carrier surfaces. Utilizing the carriers we have automated the process of separation and purification of the target proteins that had been done by manual operation previously.

We developed novel magnetic nano-carriers around 180 nm in diameter for affinity purification. Prepared magnetic nano-carriers possessed uniform core/shell/shell nano-structure composed of 40 nm magnetite particles/poly(styrene-co-glycidyl methacrylate (GMA))/polyGMA, which was constructed by admicellar polymerization. By utilizing relatively large 40 nm magnetite particles with large magnetization, the magnetic nano-carriers could show good response to permanent magnet. Thanks to uniform polymer shell with high physical/chemical stability, the magnetic nano-carriers could disperse in a wide range of organic solvent without disruption of core/shell structure and could immobilize various kinds of drugs. We examined affinity purification using our prepared magnetic nano-carriers with anti-cancer agent methotrexate (MTX) as ligand. Our magnetic nano-carriers showed higher performance compared to commercially available magnetic beads in terms of purification efficiency of target including extent of non-specific binding protein.

Despite the wide utility of ferrite nanoparticles (FP), a methodology to conjugate heterologous molecules to FP is still limited and characterization of small molecule-conjugated FP is not well known. Here, we describe what kinds of proteins and amino acids are selectively immobilized onto FP when FP is synthesized in the presence of these molecules. Two-dimentional gel electrophoresis (2D SDS-PAGE) showed that proteins with low pI value were selectively bound to FP. Quantitative analyses using HPLC suggested that L-aspartic acid (Asp) and L-cysteine (Cys) were bound to FP selectively among natural amino acids examined. Additional analysis of compounds-conjugated FP revealed that selective binding of Asp to FP was attributed with its molecular structure. It was found that the substructure of amino acid-bound to FP specifically was composed of a defined chelation of two carboxyl groups separated by two carbon atoms as deduced from FT-IR measurement. Thus, we concluded that molecules possessing two carboxyl groups separated by two carbons were bound to FP spontaneously and selectively, which might enable the attachment of free functional groups onto the FP surface if their molecules have functional groups other than carboxyl groups. The resulting complex might be applicable as a chemical tag to immobilize various molecules onto FP.

Under neutral conditions (pH=7-9) and temperature as low as 4°C we successfully synthesized ferrite nanoparticles with an intermediate structure between Fe3O4 and γ -Fe2O3 from an aqueous solution. These experimental conditions enabled us to immobilize even very unstable bioactive molecules onto the surfaces of the ferrite nanoparticles during their synthesis. The bioactive molecules were strongly fixed onto the ferrite surface intermediated by specific amino-acids or related-structure molecules each having pairs of carboxyl (COOH) groups. The COOH group pair was found to make a chemical bond with the ferrite particles. Utilizing the strong bond between such molecules and ferrites, we successfully prepared bioactive ferrite nanobeads where the ferrite nanoparticles were encapsulated in a polymer that exhibited negligible non-specific absorption of proteins. We also succeeded in fixing bioactive molecules onto the surfaces of the polymer coating of the ferrite nanobeads. We describe promising applications of our novel bioactive ferrite nanobeads such as high performance magnetic carriers for bio-screening, hypothermia, MRI contrast enhancement and magnetic drug delivery.

Direct observation of sulfur sites for sulfur-containing compounds (cysteine and its oxidative derivatives) on ferrite nanoparticles (FP) was performed by X-ray adsorption near edge structure (XANE...