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(equation presented) A unique calix[4]arene lower-rim intramolecular rearrangement, resulting in molecular asymmetry arising from the upper- and lower-rim substitution pattern, produces a new class of inherently chiral calix[4]arenes in a partial cone conformation. This was aided by molecular rigidification arising from π-π and C-H⋯π interactions between bulky lower-rim substituents, with the corresponding circular dichroism spectra exhibiting the most intense bisignate Cotton effects yet observed for calix[4]arenes not bearing a chiral center.

Upon shift-up in temperature, mouse tsFS20 mutant cells with thermolabile ubiquitin-activating enzyme E1 immediately stopped DNA replication and showed cell cycle arrest in S-phase. In contrast, when the cells were permeabilized with lysolecithin after culture at the nonpermissive temperature, they exhibited a normal level of replicative DNA synthesis in vitro. In agreement with this, intracellular pools of deoxyribonucleoside triphosphates were significantly reduced in the cells cultured at the nonpermissive temperature. Even under the permissive conditions, tsFS20 cells were more sensitive to hydroxyurea and alkylating agents, and induced less mutation than the wild-type cells. These results suggest that the ubiquitin system affects DNA replication and repair.

Excellent direct separation of various carboxylic acid and amine enentiomers was accomplished by HPLC on reversed-phase silica gels coated with copper(II) complexes of N,S-dioctyl- d -penicillamine and ( R , R )-tartaric acid mono-( R )-1-( α -naphthyl)ethylamide. The chiral recognition mechanism is discussed. These copper(II) complexes are promising as chiral stationary phases for the separation of a variety of racemic carboxylic acids and amines in which copper(II) complex formation can be assumed.

The chromatographic properties of urea derivatives derived from ( S )- and ( R )-1-( α -naphthyl)ethylamine with ( S )-valine, ( S )- tert .-leucine, ( S )-proline and ( S )-indoline-2-carboxylic acid bonded to 3-aminopropylsilica gel as chiral stationary phases were examined by HPLC to investigate the effect of the structure of the amino acid moiety. The specific enantiomer separation of various racemic compounds including alcohols, esters, amines, amino alcohols, carboxylic acids and amino acids was accomplished on these phases using normal mobile phases. The effect of the stereochemical structure in these urea derivatives on chiral recognition is discussed.

For the separation of carboxylic acid enantiomers by HPLC, the chromatographic properties of four chiral amide and urea derivatives [ N -3,5- dinitrobenzoyl - d -1-(α- naphthyl)glycine , 3,5- dinitrophenylaminocarbonyl - d - phenylglycine , 3,5- dinitrophenylaminocarbonyl - l - valine and 3,5- dinitrophenylaminocarbonyl - l -tert.- leucine ] covalently bonded to 3-aminopropylsilanized silica gel as chiral stationary phases were examined. Direct separation of various carboxylic acid enantiomers was accomplished with these chiral stationary phases. The influence of the composition of the mobile phase in these enantiomer separations was shown. Amino acid enantiomers were also well resolved in the form of their derivatives containing a free carboxylic acid group, such as tert.-butoxycarbonyl (t-BOC), benzyloxycarbonyl (Z), 9-fluorenylmethoxycarbonyl (FMOC) and 5-dimethylamino-1-naphthalenesulfonyl (dansyl) derivatives.

Three mono-amide derivatives of (R,R)-tartaric acid derived from (R)-1 -(α-naphthyl)ethylamine (I), (S)-valine-(S)-1-(α-naphthyl)ethylamide (II) and (R)-valine--(R)-1-(α-naphthyl)ethylamide (III) were prepared and their chromatographic properties as chiral selectors were examined by HPLC. The enantiomeric separation of derivatives of racemic amino acids, amines, carboxylic acids and alcohols was achieved with these chiral selectors ionically bonded to 3-aminopropyl silica gel using organic mobile phases. In this separation the chiral amine or amino acid amide moiety may play an important role in chiral recognition. On the other hand, the direct separation of racemic amino acids and hydroxy acids was accomplished with these chiral selectors in the form of copper(II) complexes coated on the reversed-phase materials using aqueous mobile phases containing copper(II) ions. In this separation the (R,R)-tartaric acid moiety may contribute to the chiral recognition. These results clearly show that these (R,R)-tartaric acid mono-amide derivatives can act as bifunctional chiral selectors, and they are promising for the enantiomeric separation of a wide range of racemic compounds by HPLC.

Copper(II) complexes of Schiff bases of chiral amino alcohols were examined as chiral ligand-exchange phases for high-performance liquid chromatography. The direct separation of a large number of amino alcohol, amine, amino acid and hydroxy acid enantiomers was accomplished using octadecylsilanized silica coated with the binuclear copper(II) complex of N-salicylidene-( R )-2-amino-1,1-bis(2-butoxy-5- tert. -butylphenyl)-3-phenyl-1-propanol ( 1 ) and water or water—organic eluents containing copper(II) ion as mobile phases. The interaction of various enantiomers with the copper(II) complex 1 for chiral discrimination was discussed.

Intracellular interferons (IFNs) exert biological functions similar to those of extracellular IFNs, but the signal transduction pathway triggered by the intracellular ligands has not been fully revealed. We investigated the signaling cascade by sequence-specific knockdown of signaling molecules by means of the RNA interference. Truncated IFN-beta gene was constructed so that the N-terminal secretory signal sequence was deleted (SD.IFN-beta). Cells transfected with this construct showed phosphorylation and activation of the STAT1 without any detectable secretion of the cytokine. The MHC class I expression was significantly augmented, while the augmentation was suppressed by short interfering RNA duplexes specific for JAK1, TYK2, and IFN-alpha/beta receptor (IFNAR) 1 and 2c chains. The SD.IFN-beta also induced p53 and phosphorylation of p53 at Ser(15). Specific silencing of p53 abrogated the antiviral effect of SD.IFN-beta, suggesting that the tumor suppressor is critically involved in antiviral defense mediated by intracellular IFN.

The absolute asymmetric photoreaction (AAP) of racemic aliphatic amino acids, such as alanine (Ala) and leucine (Leu), by left- and right-handed circularly polarized light (l- and r-CPL) irradiation was investigated in aqueous solutions at various pHs, by using the Onuki-type polarizing undulator installed in an electron storage ring. The magnitude of the optical purity (op) generated and the enantiomer-enriching mechanism operative in the AAP were found to be entirely dependent on the ionic state (and thus pH) of the amino/carboxylic acid moieties. At pH 1, the op of Ala and Leu determined by circular dichroism (CD) spectral measurement gradually developed with CPL irradiation, according to Kagan's equation. In contrast, irradiation at pH 7 gave op's much smaller than the theoretical values predicted by Kagan's equation. However, it turned out that the photodecomposition at pH 7 produces the corresponding alpha-hydroxycarboxylic acids stereoselectively, the CD sign of which is just opposite to that of the remaining amino acid, thus affording the apparently small op. It is concluded that, irrespective of solution pH, the AAP of amino acid proceeds upon CPL irradiation. At pH 1, the photodecomposition of valine, Leu, and isoleucine occurs via a Norrish type II mechanism, which is also applicable to other amino acids possessing a gamma-hydrogen. In the case of amino acids lacking a gamma-hydrogen, such as glycine and Ala, the photodecomposition mechanism is a photodeamination/hydroxylation and a Norrish type I reaction. At pH 7, the main photoproducts were ammonia and alpha-hydroxycarboxylic acids that were produced via photodeamination.