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101.
Rationally Designed Semisynthetic Natural Product Analogues for Stabilization of 14‐3‐3 Protein–Protein Interactions 下载免费PDF全文
Sebastian A. Andrei Pim de Vink Eline Sijbesma Ling Han Prof. Luc Brunsveld Prof. Nobuo Kato Prof. Christian Ottmann Dr. Yusuke Higuchi 《Angewandte Chemie (International ed. in English)》2018,57(41):13470-13474
The natural product family of fusicoccanes are stabilizers of 14‐3‐3 mediated protein–protein interactions (PPIs), some of which possess antitumor activity. In this study, the first use of molecular dynamics (MD) to rationally design PPI stabilizers with increased potency is presented. Synthesis of a focused library, with subsequent characterization by fluorescence polarization, mutational studies, and X‐ray crystallography confirmed the power of the MD‐based design approach, revealing the potential for an additional hydrogen bond with the 14‐3‐3 protein to lead to significantly increased potency. Additionally, these compounds exert their action in a cellular environment with increased potency. The newly found polar interaction could provide an anchoring point for new small‐molecule PPI stabilizers. These results facilitate the development of fusicoccanes towards drugs or tool compounds, as well as allowing the study of the fundamental principles behind PPI stabilization. 相似文献
102.
Dr. Chisato Kato Ryo Machida Rio Maruyama Dr. Ryo Tsunashima Prof. Dr. Xiao‐Ming Ren Prof. Dr. Mohamedally Kurmoo Prof. Dr. Katsuya Inoue Dr. Sadafumi Nishihara 《Angewandte Chemie (International ed. in English)》2018,57(41):13429-13432
Continual progress has been achieved in information technology through unrelenting miniaturisation of the single memory bit in integrated ferromagnetic, ferroelectric, optical, and related circuits. However, as miniaturisation approaches its theoretical limit, new memory materials are being sought. Herein, we report a unique material exhibiting single‐molecule electric polarisation switching that can operate above room temperature. The phenomenon occurs in a Preyssler‐type polyoxometalate (POM) cluster we call a single‐molecule electret (SME). It exhibits all the characteristics of ferroelectricity but without long‐range dipole ordering. The SME affords bi‐stability as a result of the two potential positions of localisation of a Tb3+ ion trapped in the POM, resulting in extremely slow relaxation of the polarisation and electric hysteresis with high spontaneous polarisation and coercive electric fields. Our findings suggest that SMEs can potentially be applied to ultrahigh‐density memory 1 and other molecular‐level electronic devices operating above room temperature. 2 相似文献
103.
Syntheses of (+)-altholactone isolated from Goniothalamus giganteus and its C-7 epimer (+)-7-epi-altholactone, (?)-etharvensin and (+)-alumheptolide-A were achieved. The lactone ring of these compounds was constructed using Pd-catalyzed carbonylation. 相似文献
104.
Aika Kai Hikaru Kato David H. Sherman Robert M. Williams Sachiko Tsukamoto 《Tetrahedron letters》2018,59(48):4236-4240
A new prenylated indoxyl alkaloid, Amoenamide B (1), was isolated from Aspergillus amoenus NRRL 35600 along with Asperochramide A (2). Although many prenylated oxindole alkaloids, containing bicyclo[2.2.2]diazaoctane cores, have been isolated from the fungus of the genera Aspergillus and Penicillium to date, 1 is the fourth compound with the indoxyl unit containing the cores. During the structure elucidation of 1, we found that the planar structure matched to that of Speramide A (3), isolated from A. ochraceus KM007, but the reported structure of 3 was incorrect and turned out to be that of Taichunamide H (4), recently isolated from A. versicolor HDN11-84. 相似文献
105.
Dr. Tatsuki Kurokawa Dr. Shigeki Kiyonaka Dr. Eiji Nakata Dr. Masayuki Endo Shohei Koyama Emiko Mori Nam Ha Tran Huyen Dinh Dr. Yuki Suzuki Kumi Hidaka Dr. Masaaki Kawata Dr. Chikara Sato Prof. Hiroshi Sugiyama Prof. Takashi Morii Prof. Yasuo Mori 《Angewandte Chemie (International ed. in English)》2018,57(10):2586-2591
In native systems, scaffolding proteins play important roles in assembling proteins into complexes to transduce signals. This concept is yet to be applied to the assembly of functional transmembrane protein complexes in artificial systems. To address this issue, DNA origami has the potential to serve as scaffolds that arrange proteins at specific positions in complexes. Herein, we report that Kir3 K+ channel proteins are assembled through zinc‐finger protein (ZFP)‐adaptors at specific locations on DNA origami scaffolds. Specific binding of the ZFP‐fused Kir3 channels and ZFP‐based adaptors on DNA origami were confirmed by atomic force microscopy and gel electrophoresis. Furthermore, the DNA origami with ZFP binding sites nearly tripled the K+ channel current activity elicited by heterotetrameric Kir3 channels in HEK293T cells. Thus, our method provides a useful template to control the oligomerization states of membrane protein complexes in vitro and in living cells. 相似文献
106.
A Quintuple [6]Helicene with a Corannulene Core as a C5‐Symmetric Propeller‐Shaped π‐System 下载免费PDF全文
Kenta Kato Prof. Dr. Yasutomo Segawa Prof. Dr. Lawrence T. Scott Prof. Dr. Kenichiro Itami 《Angewandte Chemie (International ed. in English)》2018,57(5):1337-1341
The synthesis and structural analysis of a quintuple [6]helicene with a corannulene core is reported. The compound was synthesized from corannulene in three steps including a five‐fold intramolecular direct arylation. X‐ray crystallographic analysis revealed a C5‐symmetric propeller‐shaped structure and one‐dimensional alignment in the solid state. The enantiomers of the quintuple [6]helicene were successfully separated by HPLC, and the chirality of the two fractions was identified by CD spectroscopy. A kinetic study yielded a racemization barrier of 34.2 kcal mol?1, which is slightly lower than that of pristine [6]helicene. DFT calculations indicate a rapid bowl‐to‐bowl inversion of the corannulene moiety and a step‐by‐step chiral inversion pathway for the five [6]helicene moieties. 相似文献
107.
Izumi Sakamoto Kazuya Iwaoka Yuta Kawada Takanori Naito Kazuyoshi Makida Yuki Takeuchi Takeshi Nishii Mitsuyo Horikawa Hiroto Kaku Tetsuto Tsunoda 《Tetrahedron》2018,74(24):3052-3060
3,3-Dimethoxypropylsulfonyl (Dimps) chloride was prepared and used as a new versatile sulfonating agent for ammonia, primary and secondary amines to afford corresponding Dimps-amides in excellent yields. The resulting N-nonsubstituted and N-monosubstituted Dimps-amides, activated amines, were alkylated satisfactorily under new Mitsunobu conditions. The Dimps group was removed by treatment in aqueous solution under acidic followed by basic conditions. Furthermore, epilachnene, the defensive droplets from the Mexican bean beetle, Epilachna varivestis, was synthesized utilizing this Dimps methodology in short steps. 相似文献
108.
Takashi Mino Kohei Watanabe Takumu Akiyama Yuki Mizutani Kazuki Miura Masatoshi Hashimoto Yasushi Yoshida Masami Sakamoto 《Tetrahedron》2018,74(28):3871-3878
We previously reported the synthesis of BICMAP (1a) via 6-diphenylphosphino-2,3-dihydrobenzofuran as a key intermediate. However, we did not successfully synthesize BICMAP analogues via a similar synthetic route. Herein we report the second-generation synthesis of BICMAP and its derivatives via diethylphosphonate as a key intermediate. 相似文献
109.
A Smart Sensing Method for Object Identification Using Circularly Polarized Luminescence from Coordination‐Driven Self‐Assembly 下载免费PDF全文
Yuki Imai Yuka Nakano Prof. Tsuyoshi Kawai Dr. Junpei Yuasa 《Angewandte Chemie (International ed. in English)》2018,57(29):8973-8978
The potential use of circularly polarized luminescence for object identification in a sensor application is demonstrated. New luminescence probes using pyrene derivatives as sensor luminophores were developed. (R,R)‐Im2Py and (S,S)‐Im2Py contain two chiral imidazole moieties at 1,6‐positions through ethynyl spacers (angle between spacers ca. 180°). The probe molecules spontaneously self‐assemble into chiral stacks (P or M helicity) upon coordination to metal ions with tetrahedral coordination (Zn2+). The chiral probes display neither circular dichroism (CD) nor circularly polarized luminescence (CPL) without metal ions. However, (R,R)‐Im2Py and (S,S)‐Im2Py exhibit intense chiroptical activity (CD and CPL) upon self‐assembly with Zn2+ ions. (R,R)‐Im2Py and (S,S)‐Im2Py with chemical stimuli‐responsibility allow sensing using the CPL signal as detection output, enabling us to discriminate between a signal from the target analyte and that from non‐target species. 相似文献
110.
Nishimoto A Narita K Ohmoto S Takahashi Y Yoshizumi S Yoshida T Kado N Okezaki E Kato H 《Chemical & pharmaceutical bulletin》2001,49(9):1120-1127
A series of erythromycin A 9-O-substituted oxime ether derivatives have been synthesized and evaluated for antibacterial activity against Mycobacterium avium complex (MAC) and Staphylococcus aureus. These compounds possessed stronger in vitro activity against MAC including macrolide-resistant strains than clarithromycin (2), although in vitro antibacterial activities of these compounds were less than that of 2 against Staphylococcus aureus. Our studies found that several factors contribute to the antibacterial activity against MAC. The length and spatial orientation of the substituent at 9-position were found to significantly influenced the anti-MAC activity, especially against macrolide-resistant strains. Of all the compounds prepared, erythromycin A 9-[O-(4-phenylbutyl)oxime] (12q) and erythromycin A 9-[O-(3-phenoxypropyl)oxime] (12t) possessed 16 times stronger antibacterial activity than 2 against clarithromycin-resistant strains. Surprisingly, the minimum inhibitory concentrations (MICs) of 12q and 12t against the resistant strains were almost same as those against the susceptible strains. These results suggest that the erythromycin A 9-O-substituted oxime ether derivatives would be promising macrolide antibiotics. 相似文献