- DNA-templated synthesis of trimethine cyanine dyes: A versatile fluorogenic Reaction for sensing G-quadruplex formation
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(Figure Presented) A healthy glow: Fluorogenic peptide nucleic acids (PNAs) functionalized with indoline derivatives are used to specifically sense G-quadruplex formation. Upon hybridization of both PNAs to the singlestranded flanking arms of quadruplex DNA (see scheme), the synthesis of a trimethine cyanine dye is templated. Dye formation can be detected by the appearance of a characteristic fluorescence signal.
- Meguellati, Kamel,Koripelly, Girish,Ladame, Sylvain
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Read Online
- RGD-Porphyrin conjugates: Synthesis and potential application in photodynamic therapy
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We report a convenient solid-phase synthesis and characterisation of a new class of glycosylated porphyrins bearing the RGD tripeptide, designed for photodynamic cancer therapy. The photocytotoxicities of these compounds against the K562 leukemia cell lin
- Chaleix, Vincent,Sol, Vincent,Huang, Yi-Ming,Guilloton, Michel,Granet, Robert,Blais, Jean Claude,Krausz, Pierre
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Read Online
- Design and synthesis of triphenylphosphonium-porphyrin@xylan nanoparticles for anticancer photodynamic therapy
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Most photosensitizers (PS) suffer from a lack of water solubility and from a low selectivity toward tumor cells. Delivery systems using nanoparticles make it possible to improve PS water solubility, and also tumor targeting via the enhanced permeability a
- Bouramtane, Soukaina,Brégier, Frédérique,Bretin, Ludovic,Chaleix, Vincent,Champavier, Yves,Godard, Jérémy,Léger, David,Launay, Yann,Liagre, Bertrand,Pinon, Aline,Sol, Vincent
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- Isoindoline compound, and preparation method, pharmaceutical composition and application thereof
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The invention relates to a polysubstituted isoindoline compound represented by a general formula (I), and a preparation method, a pharmaceutical composition and an application thereof. Specifically, as a CRL4CRBNE3 ubiquitin ligase regulator with a novel structure, the polysubstituted isoindoline compound provided by the invention has stronger anti-tumor activity and an anti-tumor spectrum, and can be used for preparing medicines for treating diseases related to CRL4CRBNE3 ubiquitin ligase.
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Paragraph 0475; 0977-0980
(2020/04/17)
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- Spontaneously Blinking Fluorophores Based on Nucleophilic Addition/Dissociation of Intracellular Glutathione for Live-Cell Super-resolution Imaging
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Single-molecule localization microscopy (SMLM) allows the reconstruction of super-resolution images but generally requires prior intense laser irradiation and in some cases additives to induce blinking of conventional fluorophores. We previously introduced a spontaneously blinking rhodamine fluorophore based on an intramolecular spirocyclization reaction for live-cell SMLM under physiological conditions. Here, we report a novel principle of spontaneous blinking in living cells, which utilizes reversible ground-state nucleophilic attack of intracellular glutathione (GSH) upon a xanthene fluorophore. Structural optimization afforded two pyronine fluorophores with different colors, both of which exhibit equilibrium (between the fluorescent dissociated form and the nonfluorescent GSH adduct form) and blinking kinetics that enable SMLM of microtubules or mitochondria in living cells. Furthermore, by using spontaneously blinking fluorophores working in the near-infrared (NIR) and green ranges, we succeeded in dual-color live-cell SMLM without the need for optimization of the imaging medium.
- Morozumi, Akihiko,Kamiya, Mako,Uno, Shin-Nosuke,Umezawa, Keitaro,Kojima, Ryosuke,Yoshihara, Toshitada,Tobita, Seiji,Urano, Yasuteru
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supporting information
p. 9625 - 9633
(2020/07/25)
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- Alkyllithium Compounds Bearing Electrophilic Functional Groups: A Flash Chemistry Approach
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Flash chemistry based on flow microreactor systems allowed alkyllithiums bearing electrophilic functional groups to be successfully generated and used for subsequent reactions. The series of reactions with high reactivity was achieved by extremely accurate control over residence time in a controlled and selective manner.
- Nagaki, Aiichiro,Yamashita, Hiroki,Hirose, Katsuyuki,Tsuchihashi, Yuta,Yoshida, Jun-ichi
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supporting information
p. 4027 - 4030
(2019/02/24)
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- Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER)
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The estrogen receptor (ER) is a validated target for the treatment of estrogen receptor-positive (ER+) breast cancer. Here, we describe the design, synthesis, and extensive structure-activity relationship (SAR) studies of small-molecule ERα degraders base
- Hu, Jiantao,Hu, Biao,Wang, Mingliang,Xu, Fuming,Miao, Bukeyan,Yang, Chao-Yie,Wang, Mi,Liu, Zhaomin,Hayes, Daniel F.,Chinnaswamy, Krishnapriya,Delproposto, James,Stuckey, Jeanne,Wang, Shaomeng
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p. 1420 - 1442
(2019/01/30)
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- Control of conformation in α-helix mimicking aromatic oligoamide foldamers through interactions between adjacent side-chains
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The design, synthesis and structural characterization of non-natural oligomers that adopt well-defined conformations, so called foldamers, is a key objective in developing biomimetic 3D functional architectures. For the aromatic oligoamide foldamer family
- Arrata, Irene,Grison, Claire M.,Coubrough, Heather M.,Prabhakaran, Panchami,Little, Marc A.,Tomlinson, Darren C.,Webb, Michael E.,Wilson, Andrew J.
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p. 3861 - 3867
(2019/04/26)
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- SUPER-RESOLUTION FLUORESCENT IMAGING PROBE
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[Problem] To provide a novel fluorescent probe for super-resolution imaging that uses fluorescent light emission characteristics that originate from an intermolecular nucleophilic addition-dissociation equilibrium reaction, and to provide a super-resoluti
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Paragraph 0156; 0157; 0158; 0159
(2018/03/25)
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- Synthesis and Evaluation of a Library of Trifunctional Scaffold-Derived Compounds as Modulators of the Insulin Receptor
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We designed a combinatorial library of trifunctional scaffold-derived compounds, which were derivatized with 30 different in-house-made azides. The compounds were proposed to mimic insulin receptor (IR)-binding epitopes in the insulin molecule and bind to and activate this receptor. This work has enabled us to test our synthetic and biological methodology and to prove its robustness and reliability for the solid-phase synthesis and testing of combinatorial libraries of the trifunctional scaffold-derived compounds. Our effort resulted in the discovery of two compounds, which were able to weakly induce the autophosphorylation of IR and weakly bind to this receptor at a 0.1 mM concentration. Despite these modest biological results, which well document the well-known difficulty in modulating protein-protein interactions, this study represents a unique example of targeting the IR with a set of nonpeptide compounds that were specifically designed and synthesized for this purpose. We believe that this work can open new perspectives for the development of next-generation insulin mimetics based on the scaffold structure.
- Fabre, Benjamin,Pícha, Jan,Vaněk, Václav,Selicharová, Irena,Chrudinová, Martina,Collinsová, Michaela,?áková, Lenka,Budě?ínsky, Milo?,Jirá?ek, Ji?í
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supporting information
p. 710 - 722
(2016/12/22)
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- Bivalent inhibitors for disrupting protein surface-substrate interactions and for dual inhibition of protein prenyltransferases
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Low-molecular-weight compounds that disrupt protein-protein interactions (PPIs) have tremendous potential applications as clinical agents and as chemical probes for investigating intracellular PPI networks. However, disrupting PPIs is extremely difficult due to the large, flat interfaces of many proteins, which often lack structurally defined cavities to which drug-like molecules could bind in a thermodynamically favorable manner. Here, we describe a series of bivalent compounds that anchor to the enzyme active site to deliver a minimally sized surface-binding module to the targeted surface involved in transient PPI with a substrate. These compounds are capable of significantly inhibiting enzymatic reactions involving protein surface-substrate interaction in the single-digit nanomole range. Inhibitors of farnesyltransferase (FTase), which possesses a negatively charged local area on its α-subunit, were designed by attaching a module derived from a branched monoamine-containing gallate to a conventional active-site-directed CVTM tetrapeptide using an alkyl spacer. A significant improvement in inhibitory activity (>200-fold) against farnesylation of the K-Ras4B peptide was observed when the gallate module was attached to the CVTM tetrapeptide. Furthermore, the bivalent compounds had submicromolar inhibitory activity against geranylgeranylation of the K-Ras4B peptide catalyzed by GGTase I, which has an a-subunit identical to that of FTase. The anchoring strategy we describe would be useful for designing a new class of PPI inhibitors as well as dual enzyme inhibitors targeting common surface structures.
- Machida, Shinnosuke,Kato, Nobuo,Harada, Kazuo,Ohkanda, Junko
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supporting information; experimental part
p. 958 - 963
(2011/04/16)
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- Using benzotriazole esters as a strategy in the esterification of tertiary alcohols
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Benzotriazole esters formed in situ were found to be efficient intermediates in the esterification of tertiary alcohols using 4-(dimethylamino)pyridine (DMAP) as the base. These mild and basic reaction conditions allow the conversion of various substrates into esters in good yield
- Morales-Serna, Jose Antonio,Vera, Aline,Paleo, Ehecatl,Garcia-Rios, Erendira,Gavino, Ruben,Garcia De La Mora, Gustavo,Cardenas, Jorge
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experimental part
p. 4261 - 4267
(2011/02/25)
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- TRICYCLIC INHIBITORS OF FATTY ACID AMIDE HYDROLASE
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A series of substituted oxazole compounds having an alpha keto side chain at the 2 position and an aromatic, heteroaromatic or heterocycle substituent at the 5 position are disclosed. These compounds exhibit inhibition of fatty acid amid hydrolase and are useful for treatment of malconditions involving that enzyme.
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Page/Page column 81
(2009/01/24)
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- Structure-activity relationships of α-ketooxazole inhibitors of fatty acid amide hydrolase
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A systematic study of the structure-activity relationships of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, K, - 2.6 nM), with 5hh (aryl -3-ClPh, Ki = 900 pM) being 5-fold more potent than 2b. Conformationally restricted C2 side chains were examined, and many provided exceptionally potent inhibitors, of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated, which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, Ki = 3 nM, or 13d, 2-position OH, Ki = 8 nM) comparable in potency to 2b. Proteome-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases.
- Hardouin, Christophe,Kelso, Michael J.,Romero, F. Anthony,Rayl, Thomas J.,Leung, Donmienne,Hwang, Inkyu,Cravatt, Benjamin F.,Boger, Dale L.
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p. 3359 - 3368
(2008/02/13)
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- A new method for constructing quaternary carbon centres: Tandem rhodium-catalysed 1,4-addition/intramolecular cyclisation
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The efficient tandem rhodium-catalysed 1,4-addition/cyclisation of 1,1′-alkenes using arylzinc chlorides is described. The simple one-step synthesis of substituted cyclopentanone and cyclohexanone derivatives is performed from acyclic precursors using relatively low catalyst loadings under mild conditions. A new quaternary carbon centre is created during the cyclisation step.
- Le Notre, Jerome,Van Mele, David,Frost, Christopher G.
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p. 432 - 440
(2008/02/07)
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- Enantioselective microbial reduction of substituted acetophenones
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The chiral intermediate (S)-1-(2′-bromo-4′-fluoro phenyl)ethanol 2 was prepared by the enantioselective microbial reduction of 2-bromo-4-fluoro acetophenone 1. Organisms from genus Candida, Hansenula, Pichia, Rhodotorula, Saccharomyces, Sphingomonas and B
- Patel, Ramesh N.,Goswami, Animesh,Chu, Linda,Donovan, Mary Jo,Nanduri, Venkata,Goldberg, Steven,Johnston, Robert,Siva, Prasad J.,Nielsen, Brent,Fan, Junying,He, WeiXuan,Shi, Zhongping,Wang, Kwok Y.,Eiring, Ronald,Cazzulino, Dana,Singh, Ambarish,Mueller, Richard
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p. 1247 - 1258
(2007/10/03)
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- HYDROPHILIC, THIOL-REACTIVE CYANINE DYES AND CONJUGATES THEREOF WITH BIOMOLECULES FOR FLUORESCENCE DIAGNOSIS
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This invention relates to new fluorescence dyes from the class of cyanine dyes, especially indotricarbocyanines with an absorption and fluorescence maximum in the spectral range of 700 to 900 nm, a thiol-specific reactive group, and three, preferably four
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- Alpha-substituted thio,-oxo trifluoromethylketones as phospholipase inhibitors
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Inhibitors of the cytosolic phospholypase A2 enzymes are provided which are of use in controlling a wide variety of inflammatory diseases. The inhibitors of the present invention have the general formula where X, Z, X1, R1, R2/
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- SYNTHESIS OF A SPERMIDINE-DERIVED CONJUGATED AGENT.
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A short synthesis of a spermidine conjugating agent is presented.
- Morin, Christophe,Vidal, Michel
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p. 9277 - 9282
(2007/10/02)
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