Institute of Microbial Chemistry BIKAKEN

Shinagawa-ku, Japan

Institute of Microbial Chemistry BIKAKEN

Shinagawa-ku, Japan
SEARCH FILTERS
Time filter
Source Type

Kawada M.,Institute of Microbial Chemistry BIKAKEN
Journal of Antibiotics | Year: 2016

The tumor microenvironment comprises tumor cells surrounding normal cells and the extracellular matrix. The surrounding normal cells have critical roles in the regulation of growth and metastasis of cancers, including the maintenance of cancer stem cells and the formation of cancer metastatic niches. Recent anti-Tumor strategies targeting the tumor microenvironment have included inhibition of angiogenesis and the augmentation of immune reactions. However, in this review, we will focus on stromal cells (fibroblast-like cells), a common constituent of the tumor microenvironment. Since stromal cells regulate the growth of cancer cells positively and negatively through adhesion and secreted factors, anti-Tumor strategies should consider modulating tumor-stromal cell interactions through use of small molecules. © 2016 Japan Antibiotics Research Association All rights reserved.


Opie C.R.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN
Angewandte Chemie - International Edition | Year: 2017

A linear molecular architecture equipped with complementary three-fold hydrogen-bonding units embedded with a photoswitchable trans-tetrafluoroazobenzene moiety was synthesized. The transto cis photoisomerism of the azobenzene unit induced drastic changes in the molecular architecture as a result of intramolecular hydrogen bonding as evidenced by NMR spectroscopy and size exclusion chromatography. A minute stereogenic element in the linear trans state enabled stereoselective folding into the cis state, thus producing a globular architecture with enhanced chiroptical property. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency | Inagaki F.,Japan Science and Technology Agency | Inagaki F.,Hokkaido University
Annual Review of Biophysics | Year: 2015

The formation of the autophagosome, a landmark event in autophagy, is accomplished by the concerted actions of Atg proteins. The initial step of starvation-induced autophagy in yeast is the assembly of the Atg1 complex, which, with the help of other Atg groups, recruits Atg conjugation systems and initiates the formation of the autophagosome. In this review, we describe from a structural-biological point of view the structure, interaction, and molecular roles of Atg proteins, especially those in the Atg1 complex and in the Atg conjugation systems. © Copyright ©2015 by Annual Reviews. All rights reserved.


Suzuki H.,Institute of Microbial Chemistry BIKAKEN | Kaizuka T.,University of Tokyo | Mizushima N.,University of Tokyo | Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency
Nature Structural and Molecular Biology | Year: 2015

Atg101 is an essential component of the autophagy-initiating ULK complex in higher eukaryotes, but it is absent from the functionally equivalent Atg1 complex in budding yeast. Here, we report the crystal structure of the fission yeast Atg101-Atg13 complex. Atg101 has a Hop1, Rev7 and Mad2 (HORMA) architecture similar to that of Atg13. Mad2 HORMA has two distinct conformations (O-Mad2 and C-Mad2), and, intriguingly, Atg101 resembles O-Mad2 rather than the C-Mad2-like Atg13. Atg13 HORMA from higher eukaryotes possesses an inherently unstable fold, which is stabilized by Atg101 via interactions analogous to those between O-Mad2 and C-Mad2. Mutational studies revealed that Atg101 is responsible for recruiting downstream factors to the autophagosome-formation site in mammals via a newly identified WF finger. These data define the molecular functions of Atg101, providing a basis for elucidating the molecular mechanisms of mammalian autophagy initiation by the ULK complex. © 2015 Nature America, Inc. All rights reserved.


Noda N.N.,Institute of Microbial Chemistry BIKAKEN | Noda N.N.,Japan Science and Technology Agency | Fujioka Y.,Institute of Microbial Chemistry BIKAKEN
Cellular and Molecular Life Sciences | Year: 2015

Autophagosome formation, a landmark event in autophagy, is accomplished by the concerted actions of Atg proteins. Among all Atg proteins, Atg1 kinase in yeast and its counterpart in higher eukaryotes, ULK1 kinase, function as the most upstream factor in this process and mediate autophagy initiation. In this review, we summarize current knowledge of the structure, molecular function, and regulation of Atg1 family kinases in the initiation of autophagy. © 2015 The Author(s).


Ogawa T.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Angewandte Chemie - International Edition | Year: 2013

Confined cat works better: A self-assembling heterobimetallic catalyst, comprised of a Nd/Na/amide ligand confined in an entangled multiwalled carbon nanotube (MWNT) network, outperforms the unconfined catalyst in anti-selective catalytic asymmetric nitroaldol reactions. The confined catalyst could be used repeatedly through simple filtration, and was applied to a concise enantioselective synthesis of anacetrapib. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yin L.,Institute of Microbial Chemistry BIKAKEN | Takada H.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Angewandte Chemie - International Edition | Year: 2013

A cooperative catalyst consisting of a soft Lewis acid and a hard Brønsted base promoted the title reaction. The N-thiophosphinoyl group on the ketimines was critical to surpass the high activation barrier through the soft-soft interaction of sulfur and copper. Mannich adducts with a tetrasubstituted stereogenic center were produced with excellent diastereo- and enantioselectivities. TANIAPHOS= ferrocenyl ligand. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Weidner K.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Angewandte Chemie - International Edition | Year: 2014

The direct catalytic asymmetric aldol reaction offers efficient access to β-hydroxy carbonyl entities. Described is a robust direct catalytic asymmetric aldol reaction of α-sulfanyl 7-azaindolinylamide, thus affording both aromatic and aliphatic β-hydroxy amides with high ee values. The design of this transformation features a cooperative interplay of a soft and a hard Lewis acid, which together facilitate the challenging chemoselective enolization by a hard Brønsted base. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yin L.,Institute of Microbial Chemistry BIKAKEN | Bao Y.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Journal of the American Chemical Society | Year: 2013

Catalytic asymmetric hydrophosphonylation of aromatic and aliphatic N-thiophosphinoyl ketimines with dialkyl phosphite was efficiently promoted by as little as 0.5 mol% of catalyst loading at ambient temperature. The catalyst can be recovered for repeated use, and facile removal of the thiophosphinoyl group allowed for ready access to the phosphonic acid analogue of enantioenriched α,α-disubstituted α-amino acids. © 2013 American Chemical Society.


Hashimoto K.,Institute of Microbial Chemistry BIKAKEN | Kumagai N.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Institute of Microbial Chemistry BIKAKEN | Shibasaki M.,Japan Science and Technology Agency
Organic Letters | Year: 2014

An anti-selective catalytic asymmetric nitroaldol reaction was manifested in a continuous-flow platform. The requisite Nd/Na heterogeneous catalyst was readily prepared by self-assembly of an amide-based chiral ligand, NdO 1/5(OiPr)13/5, NaHMDS, and a multiwalled carbon nanotube without covalent linkage. A stainless-steel column filled with the Nd/Na catalyst was incorporated in a flow system to promote the nitroaldol reaction with high stereoselectivity. The flow system with the heterogeneous catalyst obviated the quenching operation, and the cooling system was minimized. © 2014 American Chemical Society.

Loading Institute of Microbial Chemistry BIKAKEN collaborators
Loading Institute of Microbial Chemistry BIKAKEN collaborators