88192-20-5Relevant academic research and scientific papers
Carba-cyclophellitols Are Neutral Retaining-Glucosidase Inhibitors
Beenakker, Thomas J. M.,Wander, Dennis P. A.,Offen, Wendy A.,Artola, Marta,Raich, Lluís,Ferraz, Maria J.,Li, Kah-Yee,Houben, Judith H. P. M.,Van Rijssel, Erwin R.,Hansen, Thomas,Van Der Marel, Gijsbert A.,Codée, Jeroen D. C.,Aerts, Johannes M. F. G.,Rovira, Carme,Davies, Gideon J.,Overkleeft, Herman S.
, p. 6534 - 6537 (2017)
The conformational analysis of glycosidases affords a route to their specific inhibition through transition-state mimicry. Inspired by the rapid reaction rates of cyclophellitol and cyclophellitol aziridine - both covalent retaining β-glucosidase inhibitors - we postulated that the corresponding carba cyclopropyl analogue would be a potent retaining β-glucosidase inhibitor for those enzymes reacting through the 4H3 transition-state conformation. Ab initio metadynamics simulations of the conformational free energy landscape for the cyclopropyl inhibitors show a strong bias for the 4H3 conformation, and carba-cyclophellitol, with an N-(4-azidobutyl)carboxamide moiety, proved to be a potent inhibitor (Ki = 8.2 nM) of the Thermotoga maritima TmGH1 β-glucosidase. 3-D structural analysis and comparison with unreacted epoxides show that this compound indeed binds in the 4H3 conformation, suggesting that conformational strain induced through a cyclopropyl unit may add to the armory of tight-binding inhibitor designs.
Photoswitchable CAR-T Cell Function In Vitro and In Vivo via a Cleavable Mediator
Zhang, Bo,Wang, Yan,Huang, Shenlong,Sun, Jiaqi,Wang, Min,Ma, Wenxiao,You, Yanbo,Wu, Ling,Hu, Jin,Song, Wei,Liu, Xudong,Li, Shengjie,Chen, Hua,Zhang, Guisheng,Zhang, Lihe,Zhou, Demin,Li, Lingjun,Zhang, Xuan
, p. 60 - 7,69 (2020/12/07)
Chimeric antigen receptor (CAR)-T-based therapeutics are a breakthrough in cancer treatment; however, they are hampered by constitutive activation, which leads to worrisome side effects. Engineering CAR-T cells to be as tightly controllable as possible remains a topic of ongoing investigation. Here, we report a photoswitchable approach that uses a mediator for the at-will regulation of CAR-T cells. This mediator carries dual folate and fluorescein isothiocyanate moieties tethered by an ortho-nitrobenzyl ester photocleavable linker. CAR-T cells were shown to be highly cytotoxic to targeted cells only in the presence of the mediator and acted in a dose-dependent manner. The toxicity of CAR-T cells can be rapidly terminated by cleavage of the mediator, and the effects of CAR-T cells can be activated again by resupplementation with the mediator without compromising tumor therapy. The approach described here provides a direction for enhancing the controllability of CAR-T cells and can likely be applied in other immunotherapies.CAR-T is a powerful technology for cancer therapy, but is largely limited by inherent controllability issues. Zhang et al. developed an accurate controllable approach based on the bond-cleavage chemistry combined with universal anti-FITC CAR-T cells, allowing the regulation of CAR-T cells in a switchable manner.
Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots
Fenlon, Edward E.,Keyes, Rebecca J.,Lockey, Stephen D.,Margolis, Elizabeth A.
supporting information, p. 2314 - 2321 (2020/10/14)
The thread-link-cut (TLC) approach has previously shown promise as a novel method to synthesize molecular knots. The modular second-generation approach to small trefoil knots described herein involves electrostatic interactions between an electron-rich bismacrocyclic host compound and electron-deficient guests in the threading step. The bis-macrocyclic host was synthesized in eight steps and 6.6% overall yield. Ammonium and pyridinium guests were synthesized in 4-5 steps. The TLC knot-forming sequence was carried out and produced a product with the expected molecular weight, but, unfortunately, further characterization did not produce conclusive results regarding the topology of the product.
Fe(III)-Catalyzed Aerobic Intramolecular N-N Coupling of Aliphatic Azides with Amines
Zhang, Yue,Duan, Dongyu,Zhong, Ying,Guo, Xin-Ai,Guo, Jiawei,Gou, Jing,Gao, Ziwei,Yu, Binxun
supporting information, p. 4960 - 4965 (2019/09/03)
An Fe(III)-catalyzed intramolecular N-N coupling of aliphatic azidoamines that forms diverse five- and six-membered semisaturated diazoheterocycles using air as an oxidant is reported, providing an alternative to hydrazine-based methods. Mechanistic studies suggest that a N-radical induced intramolecular homolytic substitution (SH2) is involved in ring closure. The power of this N-N bond-forming method is also demonstrated by using it as the final step in a total synthesis of (-)-newbouldine.
For the control of the chimeric antigen receptor of the T cell activation/inhibit the connecting arm and its application (by machine translation)
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Paragraph 0020; 0031; 0034, (2019/01/23)
The invention discloses a method for control CAR - T/inhibit the activation of the link arm, and one end of the cells containing the target [...] molecule, the other at one end and can be specific CAR - T cell identified with biological orthogonality of the part, and the middle of the can be biological orthogonal fracture chemical group coupling. This invention can realize the CAR - T cell from active to a resting state fast and flexible conversion, to CAR - T cell inhibiting the systematic and high efficiency. Adjusting has reversibility, not damage or kill some CAR - T cell, can realize the CAR - T cell from active to close and then to activate the flexible change, the overall functions of the treatment is not affected. (by machine translation)
Traceless Templated Amide-Forming Ligations
Osuna Gálvez, Alberto,Bode, Jeffrey W.
supporting information, p. 8721 - 8726 (2019/06/13)
Template assistance allows organic reactions to occur under highly dilute conditions - where intermolecular reactions often fail to proceed - by bringing reactants into close spatial proximity. This strategy has been elegantly applied to numerous systems, but always with the retention of at least one of the templating groups in the product. In this report, we describe a traceless, templated amide-forming ligation that proceeds at low micromolar concentration under aqueous conditions in the presence of biomolecules. We utilized the unique features of an acylboronate-hydroxylamine ligation, in which covalent bonds are broken in each of the reactants as the new amide bond is formed. By using streptavidin as a template and acylboronates and O-acylhydroxylamines bearing desthiobiotins that are cleaved upon amide formation, we demonstrate that traceless, templated ligation occurs rapidly even at submicromolar concentrations. The requirement for a close spatial orientation of the functional groups - achieved upon binding to streptavidin - is critical for the observed enhancement in the rate and quantity of product formed.
Novel menadione hybrids: Synthesis, anticancer activity, and cell-based studies
Prasad, Chakka Vara,Nayak, Vadithe Lakshma,Ramakrishna, Sistla,Mallavadhani, Uppuluri Venkata
, p. 220 - 233 (2017/12/29)
A series of novel menadione-based triazole hybrids were designed and synthesized by employing copper-catalyzed azide-alkyne cycloaddition (CuAAC). All the synthesized hybrids were characterized by their spectral data (1H NMR, 13C NMR, IR, and HRMS). The synthesized compounds were evaluated for their anticancer activity against five selected cancer cell lines including lung (A549), prostate (DU-145), cervical (Hela), breast (MCF-7), and mouse melanoma (B-16) using MTT assay. The screening results showed that majority of the synthesized compounds displayed significant anticancer activity. Among the tested compounds, the triazoles 5 and 6 exhibited potent activity against all cell lines. In particular, compound 6 showed higher potency than the standard tamoxifen and parent menadione against MCF-7 cell line. Flow cytometric analysis revealed that compound 6 arrested cell cycle at G0/G1 phase and induced apoptotic cell death which was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin-V-FITC assay. Thus, compound 6 can be considered as lead molecule for further development as potent anticancer therapeutic agent.
Method for producing azido-amine derivative
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Page/Page column 5; 6, (2018/03/25)
A method for producing an azido-amine derivative includes obtaining an azido-amine derivative and extracting the azido-amine derivative obtained by using an aromatic solvent or an ether solvent.
A fullerene helical peptide: synthesis, characterization and formation of self-assembled monolayers on gold surfaces
Nasrallah, Houssein,Rabah, Jad,Bui-Thi-Tuyet, Van,Baczko, Krystyna,Fensterbank, Hélène,Bourdreux, Flavien,Goncalves, Anne-Marie,Declerck, Valérie,Boujday, Souhir,Humblot, Vincent,Wright, Karen,Vallée, Anne,Allard, Emmanuel
supporting information, p. 19423 - 19432 (2018/12/13)
The synthesis of a C60-peptide using “clickable” fullerene and peptide derivatives is described. The peptide is composed of a repeating sequence of α-aminoisobutyric acid (Aib) and two l-alanine (Ala) residues, promoting the formation of a helical conformation, which has been confirmed by IR absorption, NMR and circular dichroism measurements. In addition, the presence of a lipoyl moiety, at the end of the peptide sequence, allows the formation of self-assembled monolayers of the C60-peptide and the parent peptide on a gold surface. A C60-alkyl derivative was also prepared to compare the self-assembly properties of fullerene derivatives containing peptides or alkyl chains. The fullerene assembly on a gold substrate characterized by quartz crystal microbalance and by cyclic voltammetry show that the monolayers containing alkyl chains are slightly less well packed than the peptide monolayers. Finally, polarization modulation reflection adsorption infra-red spectroscopy measurements indicate that the C60-peptide tends to be more vertical than the parent peptide which could originate from complementary C60-C60 and helical-helical interactions.
METHOD OF PRODUCING AZIDAMINE DERIVATIVES
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Paragraph 0024, (2016/10/07)
PROBLEM TO BE SOLVED: To provide a method of producing azidamine derivatives that overcome problems such as deterioration with time and safety and enables mass production on an industrial scale. SOLUTION: A method of producing azidamine derivatives comprises the steps of obtaining azidamine derivatives and extracting the obtained azidamine derivatives with an aromatic solvent or an ether solvent. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
