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481.
482.
Tai A Fujinami Y Matsumoto K Kawasaki D Yamamoto I 《Bioscience, biotechnology, and biochemistry》2002,66(8):1628-1634
The bioavailability of a series of novel acylated ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids (6-Acyl-AA-2G), as an ascorbic acid (AA) supplement was investigated in rats and guinea pigs. Oral administration of 6-Acyl-AA-2G to rats resulted in an increase in the plasma AA level. However, the intact form was not detectable in the plasma by high-performance liquid chromatography, indicating its hydrolysis through the process of absorption. After an intravenous injection to rats of 6-Octa-AA-2G as a representative derivative, the intact form rapidly disappeared from the plasma, being followed by a prolonged and marked elevation of the plasma AA level. Various tissue homogenates from guinea pigs were examined for their releasing activity of AA, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) and 6-O-acyl-AA from 6-Acyl-AA-2G. High activity was observed in the small intestine. These hydrolytic activities to AA and 6-O-acyl-AA were completely inhibited by castanospermine, an alpha-glucosidase inhibitor, and AA-2G was observed as the only resulting hydrolysate, suggesting the participation of alpha-glucosidase and esterase in the in vivo hydrolysis of 6-Acyl-AA-2G. 6-Octa-AA-2G was found to exhibit an obvious therapeutic effect in scorbutic guinea pigs from its repeated oral administration. These results indicate that 6-Acyl-AA-2G is a readily available source of AA activity in vivo, and may be useful as an effective pharmacological agent and as a promising food additive. 相似文献
483.
In this paper, we describe the synthesis of the 3'-3'-linked TFOs that can form the antiparallel triplexes with the duplex DNA target by reverse Hoogsteen hydrogen bonds. Stability of the alternate-strand triplexes between these TFOs and the target DNAs was investigated using the electrophoretic mobility shift assay (EMSA). It was found that the alternate-strand triplexes were significantly stabilized by linking the TFO fragments with the pentaerythritol linker. And, unlike the alternate-strand triplexes composed of the pyrimidine motif, the terminal ammonium ion of the aminobutyl-linker and the intercalator of the TFOs did not contribute to the stability of the alternate-strand triplex comprised of the purine motif. We also tested the ability of the 3'-3'-linked TFOs to inhibit cleavage of the duplex DNA target 17 by the restriction enzyme EcoT14I and found that the 3'-3'-linked TFOs 12 and 13 inhibited the cleavage by the enzyme more effectively than the unlinked decamer 8. Thus, the TFOs linked with pentaerythritol may be useful as the antigene oligonucleotide to the DNA targets, which have alternating oligopyrimidine-oligopurine sequences. 相似文献
484.
Hirota S Suzuki M Watanabe Y 《Biochemical and biophysical research communications》2004,314(2):452-458
Effect of a hydrophobic peptide on folding of oxidized cytochrome c (cyt c) is studied with trityrosine. Folding of cyt c was initiated by pH jump from 2.3 (acid-unfolded) to 4.2 (folded). The Soret band of the 2-ms transient absorption spectrum during folding decreased its intensity and red-shifted from 397 to 400 nm by interaction with trityrosine, whereas tyrosinol caused no significant effect. The change in the transient absorption spectrum by interaction with trityrosine was similar to that obtained with 100 mM imidazole, which showed that the population of the intermediate His/His coordinated species increased during folding of cyt c by interaction with trityrosine. The absorption change was biphasic, the fast phase (82+/-9s(-1)) corresponding to the transition from the His/H(2)O to the His/Met coordinated species, whereas the slow phase (24+/-3s(-1)) from His/His to His/Met. By addition of trityrosine, the relative ratio of the slow phase increased, due to increase of the His/His species at the initial stage of folding. According to the resonance Raman spectra of cyt c, the high-spin 6-coordinate and low-spin 6-coordinate species were dominated at pH 2.3 and 4.2, respectively, and these species were not affected by addition of trityrosine. These results demonstrated that the His/His species increased by interaction with trityrosine at the initial stage of cyt c folding, whereas the heme coordination structure was not affected by trityrosine when the protein was completely unfolded or folded. Hydrophobic peptides thus may be useful to study the effects of hydrophobic interactions on protein folding. 相似文献
485.
486.
Matsumoto S Tanimoto T Yoshida S Ikeda M Takeda M Saiki C Shimazu Y Aoba T Nasu M Suzuki K 《Chemical senses》2004,29(4):351-361
Inhibitory responses of slowly adapting pulmonary stretch receptor (SAR) activity to CO(2) inhalation (maximal tracheal CO(2) concentration ranging from 9.5 to 12.5%) for approximately 60 s were examined before and after administration of acetazolamide (a carbonic anhydrase inhibitor) or 4-aminopyridine (4-AP, a K(+) channel blocker). The experiments were performed in 35 anesthetized, artificially ventilated rats after unilateral vagotomy. Sixty-eight of eighty-four SARs were inhibited by CO(2) inhalation. The SAR inhibition was attenuated by pretreatment with either acetazolamide (20 mg/kg, n = 10) or 4-AP (0.7 and 2.0 mg/kg, n = 10). In other series of experiments, stainings to show the existence of carbonic anhydrase (CA) enzymatic reaction were not found in the smooth muscle of either extrapulmonary or intrapulmonary bronchi. Protein gene product 9.5 (PGP 9.5)-immunoreactive SAR terminals to form leaflike extensions were found in the bronchioles at different diameters and were smooth-muscle-related receptors. But in the same sections, CA isozyme II-like (erythrocyte CA) immunoreactive SAR terminals were not identified. These results suggest that CO(2)-induced inhibition of SARs may be involved in the CA-dependent CO(2) hydration in addition to the activation of 4-AP sensitive K(+) currents. 相似文献
487.
The noncovalent chiral domino effect (NCDE), defined as chiral interaction upon an N-terminus of a 3(10)-helical peptide, will provide a unique method for structural control of a peptide helix through the use of external chirality. On the other hand, the NCDE has not been considered to be effective for the helicity control of peptides strongly favoring a one-handed screw sense. We here aim to promote the NCDE on peptide helicity using two types of nonapeptides: H-beta-Ala-Delta(Z)Phe-Aib-Delta(Z)Phe-X-(Delta(Z)Phe-Aib)(2)-OCH(3) [Delta(Z)Phe = alpha,beta-didehydrophenylalanine, Aib = alpha-aminoisobutyric acid], where X as the single chirality is L-leucine (1) or L-phenylalanine (2). NMR, IR, and CD spectroscopy as well as energy calculation revealed that both peptides alone form a right-handed 3(10)-helix. The original CD amplitudes or signs in chloroform, irrespective of a strong screw-sense preference in the central chirality, responded sensitively to external chiral information. Namely added Boc-L-amino acid stabilized the original right-handed helix, while the corresponding d-isomer destabilized it or transformed it into a left-handed helix. These peptides were also shown to bind more favorably to an L-isomer from the racemate. Although similar helicity control was observed for analogous nonapeptides bearing an N-terminal Aib residue (Inai, Y.; et al. Biomacromolecules 2003, 4, 122), the present findings demonstrate that the N-terminal replacement by the beta-Ala residue significantly improves the previous NCDE to achieve more effective control of helicity. Semiempirical molecular orbital calculations on complexation of peptide 2 with Boc-(L or D)-Pro-OH reasonably explained the unique conformational change induced by external chirality. 相似文献
488.
In this paper, we describe the synthesis of the 3'-3'-linked oligonucleotides connected with pentaerythritol composed of asymmetrical sequences. Stability of the triplexes between these oligonucleotides and the DNA targets involving the adjacent oligopurine domains on alternate strands was investigated using the electrophoretic mobility shift assay (EMSA) and DNase I footprinting experiment. It was found that the 3'-3'-linked oligonucleotides composed of asymmetrical sequences formed the stable antiparallel triplexes with the DNA targets as compared with the unlinked oligonucleotides. Thus, oligonucleotides linked with pentaerythritol would be useful as antigene oligonucleotides for DNA targets consisting of the alternating oligopyrimidine-oligopurine sequences. 相似文献
489.
The T cell cytokines profoundly modify the phenotypic and functional characteristics of keratinocytes. Until now, no study has focused on the effect of Th1 and Th2 cytokines on keratinocyte permeability. Using a two-layer well culturing system, permeability was assessed through cultured keratinocyte sheet in the presence or absence of various concentrations of IFN-gamma and IL-4. Transepithelial electrical resistance (TER) and the flux of 40 kDa FITC-dextrans were measured across the cultured keratinocyte sheet. IFN-gamma significantly increased the TER in a dose- and time-dependent manner, suggesting that IFN-gamma profoundly inhibited the permeability of ions through the keratinocyte sheet. In contrast, IL-4 did not affect the TER. When compared to medium control, the flux of FITC-dextran of the IFN-gamma group was significantly decreased in a dose-dependent fashion. In sharp contrast, the flux of FITC-dextran was significantly and dose-dependently increased in the presence of IL-4. A significant increase in TER and a significant decrease in the flux of dextran suggested that IFN-gamma clearly reduced the permeability of both ions and high molecular weight material through the keratinocyte sheet. Although IL-4 did not affect the permeability of the ions, it significantly enhanced the permeability of high molecular weight material. A flow cytometric assay revealed that the expression of desmoglein-3 was suppressed by IL-4, but was enhanced by IFN-gamma. The reciprocal regulation of permeability of the cultured keratinocyte sheet by IFN-gamma and IL-4 may be partly related to the modification of intercellular adhesion molecules. 相似文献
490.
Chiral interaction of helical peptide with chiral molecule, and concomitant induction in its helix sense have been demonstrated in optically inactive nonapeptide (1) possessing Gly at its N-terminus: H-Gly-(Delta(Z)Phe-Aib)(4)-OCH(3) (1: Delta(Z)Phe = Z-dehydrophenylalanine; Aib = alpha-aminoisobutyric acid). Spectroscopic measurements [mainly nuclear magnetic resonance (NMR) and circular diochroism (CD)] as well as theoretical simulation have been carried out for that purpose. Peptide 1 in the 3(10)-helix tends to adopt preferentially a right-handed screw sense by chiral Boc-L-amino acid (Boc: t-butoxycarbonyl). Induction in the helix sense through the noncovalent chiral domino effect should be derived primarily from the complex supported by the three-point coordination on the N-terminal sequence. Thus the 3(10)-helical terminus consisting of only alpha-amino acid residues enables chiral recognition of the Boc-amino acid molecule, leading to modulation of the original chain asymmetry. Dynamics in the helix-sense induction also have been discussed on the basis of a low-temperature NMR study. Furthermore, the inversion of induced helix sense has been achieved through solvent effects. 相似文献