-
[show abstract]
[hide abstract]
ABSTRACT: 1,2,5-Thiadiazole improved RNA separation with in-capillary denaturing polymer electrophoresis. 1,2,5-Thiadiazole was synthesized as an extraction solvent substituted for a halogenated solvent. While 1,2,5-thiadiazole was an excellent extraction solvent and an environmentally friendly solvent, we found that 1,2,5-thiadiazole was a strong hydrophobic compound for RNA and the RNA separation performance by in-capillary denaturing polymer electrophoresis was dramatically improved. We suggest "in-capillary denaturing polymer electrophoresis" as an RNA separation that realizes the denaturing and separation simultaneously. RNA separation by the method required a strong denaturant, acetic acid, to cleave the intramolecular hydrogen. The running buffer containing acetic acid was of high conductivity and low pH, in which the condition introduced Joule heating and low sensitivity. While conventional denaturants, formaldehyde and urea, maintained small electric conductivity and neutral pH, these denaturants were too weak to achieve the RNA separation by in-capillary denaturing polymer electrophoresis. 1,2,5-Thiadiazole being a neutral molecule, both conductivity and buffer pH were able to be adjusted to a desirable strength for RNA separation. In this paper, we report that RNA separation by in-capillary denaturing polymer electrophoresis in neutral pH was achieved and the sensitivity for RNA separation was higher than that for RNA separation by in-capillary denaturing polymer electrophoresis with acetic acid.
Journal of Separation Science 09/2011; 34(20):2901-5. · 2.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The total synthesis of lactonamycin has been achieved. The synthesis includes sequential intramolecular conjugate addition of alcohols to the acetylenic ester, stereoselective glycosylation of the tertiary alcohol, and Michael–Dieckmann type cyclization with the thioester, by which the highly convergent route has been established.
Tetrahedron Letters - TETRAHEDRON LETT. 01/2010; 51(42):5546-5549.
-
The Journal of Antibiotics 08/2009; 62(8):469-70. · 1.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Actinopyrone A, an anti-Helicobacter pylori agent, was synthesized in nine steps from a silyl dienol ether. A vinylogous anti-aldol was stereoselectively synthesized by our developed remote stereoinduction methodology; coupling of this with a sulfone and a phosphonate species led to the construction of a vinylpyrone compound. This was submitted to reductive de-conjugation to give actinopyrone A. The absolute stereochemistry of actinopyrone A was determined to have the configuration 14R,15R.
Chemistry - An Asian Journal 09/2008; 3(8-9):1415-21. · 4.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The salmon peptide digested from salmon muscle showed a strong inhibitory activity against the angiotensin I-converting enzyme (ACE). The antihypertensive effect of the salmon peptide on spontaneously hypertensive rats (SHR) was examined. After the single intravenous administration of the salmon peptide at a dose of 30 mg/kg body weight, the systolic blood pressure (SBP) was significantly reduced against the control. Further, a double-blind, placebo-controlled, parallel-group study determined the efficacy of the salmon peptide in mild hypertensive subjects. The SBP, after a 1.0 g of salmon peptide intake, was significantly reduced at 4 weeks after the intake, and 2 weeks after the intake finished, compared to the value before ingestion. Bioassay-guided separation of the salmon peptide, using a combination of column chromatographic techniques, led to the identification of 20 active di- and tri-peptides, including Ile-Val-Phe and Phe-Ile-Ala as two new ACE inhibitory tripeptides. Ile-Trp had the strongest ACE inhibitory activity (IC50 = 1.2 μM) in vitro, and contributed 5.2% to the total ACE inhibitory activity. The salmon peptide and Ile-Trp showed a digestive resistance by in vitro assay, which mimicked the digestive organ, and had no affinity for factors related to blood pressure regulation, except for the ACE inhibitory activity.
Fisheries Science 08/2008; 74(4):911 - 920. · 0.94 Impact Factor
-
Noritaka Yamaguchi,
Tetsunari Oyama,
Emi Ito,
Hitoshi Satoh,
Sakura Azuma,
Mitsuhiro Hayashi,
Ken Shimizu,
Reiko Honma,
Yuka Yanagisawa,
Akira Nishikawa,
Mika Kawamura,
Jun-ichi Imai,
Susumu Ohwada, Kuniaki Tatsuta,
Jun-Ichiro Inoue,
Kentaro Semba,
Shinya Watanabe
[show abstract]
[hide abstract]
ABSTRACT: ErbB2-negative breast tumors represent a significant therapeutic hurdle because of a lack of effective molecular targets. Although NOTCH proteins are known to be involved in mammary tumorigenesis, the functional significance of these proteins in ErbB2-negative breast tumors is not clear. In the present study, we examined the expression of activated NOTCH receptors in human breast cancer cell lines, including ErbB2-negative and ErbB2-positive cell lines. Activated NOTCH1 and NOTCH3 proteins generated by gamma-secretase were detected in most of the cell lines tested, and both proteins activated CSL-mediated transcription. Down-regulation of NOTCH1 by RNA interference had little or no suppressive effect on the proliferation of either ErbB2-positive or ErbB2-negative cell lines. In contrast, down-regulation of NOTCH3 significantly suppressed proliferation and promoted apoptosis of the ErbB2-negative tumor cell lines. Down-regulation of NOTCH3 did not have a significant effect on the ErbB2-positive tumor cell lines. Down-regulation of CSL also suppressed the proliferation of ErbB2-negative breast tumor cell lines, indicating that the NOTCH-CSL signaling axis is involved in cell proliferation. Finally, NOTCH3 gene amplification was detected in a breast tumor cell line and one breast cancer tissue specimen even though the frequency of NOTCH3 gene amplification was low (<1%). Taken together, these findings indicate that NOTCH3-mediated signaling rather than NOTCH1-mediated signaling plays an important role in the proliferation of ErbB2-negative breast tumor cells and that targeted suppression of this signaling pathway may be a promising strategy for the treatment of ErbB2-negative breast cancers.
Cancer Research 03/2008; 68(6):1881-8. · 7.86 Impact Factor
-
Kuniaki Tatsuta
[show abstract]
[hide abstract]
ABSTRACT: The first total synthesis and development of a variety of bioactive natural products have been accomplished by using carbohydrates as a chiral source. In addition, practically useful intermediates have been created, analogs of natural products have been prepared, their structure-activity relationships studied, and the large-scale preparations of medicinally useful compounds established. The key target molecules have been the "Big Four" antibiotics (macrolides, aminoglycosides, beta-lactams and tetracyclines), pyranonaphthoquinone antibiotics, glycosidase inhibitors, and a side-chain of cephem antibiotics.
Proceedings of the Japan Academy Ser B Physical and Biological Sciences 02/2008; 84(4):87-106. · 2.77 Impact Factor
-
Noritaka Yamaguchi,
Emi Ito,
Sakura Azuma,
Reiko Honma,
Yuka Yanagisawa,
Akira Nishikawa,
Mika Kawamura,
Jun-Ichi Imai, Kuniaki Tatsuta,
Jun-Ichiro Inoue,
Kentaro Semba,
Shinya Watanabe
[show abstract]
[hide abstract]
ABSTRACT: The forkhead transcription factor FoxA1 is thought to be involved in mammary tumorigenesis. However, the precise role of FoxA1 in breast cancer development is controversial. We examined expression of FoxA1 in 35 human breast cancer cell lines and compared it with that of ErbB2, a marker of poor prognosis in breast cancer. We found that FoxA1 is expressed at high levels in all ErbB2-positive cell lines and a subset of ErbB2-negative cell lines. Down-regulation of FoxA1 by RNA interference significantly suppressed proliferation of ErbB2-negative and FoxA1-positive breast cancer cell lines. Down-regulation of FoxA1 also enhanced the toxic effect of Herceptin on ErbB2-positive cell lines through induction of apoptosis. Taken together with previous data that FoxA1 is a marker of luminal cells in mammary gland, our present results suggest that FoxA1 plays an important role as a lineage-specific oncogene in proliferation of cancer cells derived from mammary luminal cells.
Biochemical and Biophysical Research Communications 02/2008; 365(4):711-7. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Asymmetric vinylogous aldol reaction is a powerful methodology to introduce a multi functional group in the stereoselective manner. Recently, we have developed highly stereoselective vinylogous Mukaiyama aldol reactions using vinylketene N,O-acetals possessing the chiral oxazolidone. Our methodology has been applied to the asymmetric syntheses of natural products to establish the short and efficient routes. This review focuses on the asymmetric vinylogous Mukaiyama aldol reactions using vinylketene N,O-acetals in total syntheses of natural products.
Mini-Reviews in Organic Chemistry 01/2008; 5(1):1-18. · 2.41 Impact Factor
-
Fumito Koizumi,
Naomi Fukumitsu,
Jinrong Zhao,
Ruthada Chanklan,
Tokichi Miyakawa,
Shoko Kawahara,
Shin Iwamoto,
Makoto Suzuki,
Shingo Kakita,
Endang S Rahayu,
Seijiro Hosokawa, Kuniaki Tatsuta,
Michio Ichimura
[show abstract]
[hide abstract]
ABSTRACT: In the course of screening for drugs that suppress the Ca(2+)-mediated growth inhibition in a yeast mutant, we found that the metabolite of Fusarium sp. strain YCM1008 inhibited Ca(2+)-signaling. A novel pyrano-pyridone, YCM1008A was isolated from the fermentation broth using HLB column chromatography followed by HPLC, and the structure was elucidated by spectral analysis. YCM1008A suppressed Ca(2+)-induced growth inhibition of the Saccharomyces cerevisiae (Deltazds1Deltasyr1) mutant.
The Journal of Antibiotics 08/2007; 60(7):455-8. · 1.65 Impact Factor
-
Chemistry Letters - CHEM LETT. 01/2007; 36(1):10-11.
-
[show abstract]
[hide abstract]
ABSTRACT: Xanthocillin derivatives, which show thrombopoietin receptor agonist activity, were synthesized through our developed method. Bioassay data suggest the importance of alkene geometry, the presence of substituents at the benzene ring that support hydrophobic character, and the moderate size of the molecule. One of the two isonitrile group of the natural product appears to be dispensable.
The Journal of Antibiotics 12/2006; 59(11):729-34. · 1.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent progress of total syntheses in our laboratory has been described along with our background and methodologies. The target bioactive polyketides are classified into three categories according to their structures: (i) lactone-fused polycyclic compounds [(+)-cochleamycin A, (+)-tubelactomicin A, and (-)-tetrodecamycin], (ii) aromatic compounds [(-)-tetracycline, (-)-BE-54238B, lymphostin, and (-)-lagunamycin], and (iii) acyclic polyketides [xanthocillin X dimethylether, (+)-trichostatin D, and (+)-actinopyrone A]. Features of the total syntheses are described. Original methodologies have been developed and applied to construct the inherent structures of the target molecules. Most syntheses cited herein are the first total syntheses, and the absolute structures of the target molecules have been determined.
The Chemical Record 02/2006; 6(4):217-33. · 4.38 Impact Factor
-
Chemical Reviews 01/2006; 105(12):4707-29. · 40.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lagunamycin (1) has been synthesized by using our developed remote stereoinduction, Knorr condensation, periodinane oxidation, and diazonation. This enantioselective synthesis determined the absolute configuration of lagunamycin. Existence of rotational conformers was confirmed by NMR studies.
Tetrahedron Letters - TETRAHEDRON LETT. 01/2006; 47(35):6183-6186.
-
[show abstract]
[hide abstract]
ABSTRACT: (−)-Tetrodecamycin (1) has been synthesized from optically active butenolide through stereoselective SmI2-mediated pinacol cyclization and newly developed deoxygenation.
Tetrahedron Letters - TETRAHEDRON LETT. 01/2006; 47(21):3595-3598.
-
The Journal of Antibiotics 05/2004; 57(4):291-7. · 1.65 Impact Factor
-
ChemInform 11/2003; 34(48).
-
The Journal of Antibiotics 07/2003; 56(6):584-90. · 1.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The proline-rich motif in proteins is known to function as a ligand sequence that binds to protein modules such as SH3, WW, and several other protein interaction domains. These proline-rich ligand-mediated protein-protein interactions (abbreviated PLPI) are important in many signaling pathways that are involved in various diseases. Our previous studies showed that UCS15A, produced by Streptomyces species, inhibited PLPI. Here we report on synthetic analogs of UCS15A that show more potent activity than UCS15A in inhibiting PLPI. A synthetic analog, compound 2c, blocked in vitro PLPI of Sam68-Fyn-SH3 as well as in vivo PLPI of Grb2-Sam68 and Grb2-Sos1. Activation of MEK was also inhibited by compound 2c. Unlike UCS15A, compound 2c was an order of magnitude less cytotoxic and did not cause morphological changes in treated cells.
Chemistry & Biology 06/2003; 10(5):443-51. · 5.83 Impact Factor
