- Solvent-Driven Supramolecular Wrapping of Self-Assembled Structures
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Self-assembly relies on the ability of smaller and discrete entities to spontaneously arrange into more organized systems by means of the structure-encoded information. Herein, we show that the design of the media can play a role even more important than
- Moreno-Alcántar, Guillermo,Aliprandi, Alessandro,Rouquette, Remi,Pesce, Luca,Wurst, Klaus,Perego, Claudio,Brüggeller, Peter,Pavan, Giovanni M.,De Cola, Luisa
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Read Online
- Synthesis of water-soluble, ester-terminated dendrons and dendrimers containing internal PEG linkages
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Dendrimers up to three generations, possessing internal PEG units within the branching framework, were synthesized by a convergent approach via the reaction of amine-based dendrons 6, 9, and 11 with 6,6-bis(4-chlorocarbonyl-2- oxabutyl)-4,8-dioxaundecane-1,11-dicarbonyl chloride. These new constructs were fully characterized, shown to exhibit good solubilities in organic as well as aqueous solvents, and demonstrated to solubilize lithium triflate salts in nonaqueous environments, such as chloroform.
- Newkome, George R.,Kotta, Kishore K.,Mishra, Amaresh,Moorefield, Charles N.
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Read Online
- Tailoring carbon nanotube surfaces with glyconanorings: New bionanomaterials with specific lectin affinity
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Remarkably stable, water-soluble glyconanoring-coated SWCNTs were prepared by self organization and photopolymerization of neutral diacetylene-based glycolipids on the nanotube surface; the nanoconstructs are able to engage in specific ligand-lectin interactions in a similar way to glycoconjugates on cell membranes.
- Khiar, Noureddine,Leal, Manuel Pernia,Baati, Rachid,Ruhlmann, Christine,Mioskowski, Charles,Schultz, Patrick,Fernandez, Inmaculada
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Read Online
- Design, synthesis and activity study of a novel PI3K degradation by hijacking VHL E3 ubiquitin ligase
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PI3K kinase plays an important role in regulating key processes in cells, such as cell growth, metabolism, proliferation, and apoptosis. The overexpression of PI3K kinase exists in many cancers. The proteolytic target chimera (PROTAC) technology is a new technology that uses the ubiquitin–proteasome system to degrade a given target protein. It has been described that CRBN-based PROTAC targets the degradation of PI3K kinase. However, PROTAC based on VHL has not been reported yet. Here, we connected the previously obtained highly active PI3K inhibitor to the VHL ligand through different small molecules, and obtained a series of PROTAC molecules targeting PI3K kinase. Obtain the most active compound through screening. It provides evidence for the feasibility of PROTAC technology to recruit VHL E3 ligase in PI3K kinase.
- Li, Chuchu,Liu, Xiaoqing,Ma, Mingliang,Wang, Haili
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- ANTIBODY-DRUG CONJUGATES COMPRISING ANTI-B7-H3 ANTIBODIES
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The present disclosure relates to antibody-drug conjugates (ADCs) wherein one or more active agents are conjugated to an anti-B7-H3 antibody through a linker. The linker may comprise a unit that covalently links active agents to the antibody. The disclosure further relates to monoclonal antibodies and antigen binding fragments, variants, multimeric versions, or bispecifics thereof that specifically bind B7-H3, as well as methods of making and using these anti-B7-H3 antibodies and antigen-binding fragments thereof in a variety of therapeutic, diagnostic and prophylactic indications
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Page/Page column 106; 108-109
(2022/01/04)
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- GPX4 protein degradation agent, preparation method and application thereof, and antitumor cell drug
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The invention provides a GPX4 protein degradation agent, a preparation method thereof, and an anti-tumor cell drug, and belongs to the technical field of drug application. The GPX4 protein degradation agent provided by the invention has a protein degradation targeting chimera (PROTAC) molecular structure, a mother nucleus structure of the GPX4 protein degradation agent is used as a small molecule ligand for combining target protein, an A2 substituent is used as a small molecule ligand for combining an E3 ubiquitin ligase compound, and an A1 substituent is used as a connecting group for connecting the two ligands. The GPX4 protein degradation agent with the structure can specifically recognize GPX4 protein and effectively ubiquitinate and degrade the GPX4 protein, so that tumor cell ferroptosis is induced.
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Paragraph 0317-0318; 0331-0332
(2021/09/04)
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- Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction
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The antibody pretargeting approach for radioimmunotherapy (RIT) using inverse electron demand Diels-Alder cycloaddition (IEDDA) constitutes an emerging theranostic approach for solid cancers. However, IEDDA pretargeting has not reached clinical trial. The major limitation of the IEDDA strategy depends largely on trans-cyclooctene (TCO) stability. Indeed, TCO may isomerize into the more stable but unreactive cis-cyclooctene (CCO), leading to a drastic decrease of IEDDA efficiency. We have thus developed both efficient and reproducible synthetic pathways and analytical follow up for (PEGylated) TCO derivatives, providing high TCO isomeric purity for antibody modification. We have set up an original process to limit the isomerization of TCO to CCO before the mAbs’ functionalization to allow high TCO/tetrazine cycloaddition.
- Béquignat, Jean-Baptiste,Boucheix, Claude,Canitrot, Damien,Chezal, Jean-Michel,Degoul, Fran?oise,Miot-Noirault, Elisabeth,Moreau, Emmanuel,Navarro-Teulon, Isabelle,Quintana, Mercedes,Rondon, Aurélie,Taiariol, Ludivine,Ty, Nancy
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supporting information
(2020/07/21)
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- Self-Adjuvanting Cancer Vaccines from Conjugation-Ready Lipid A Analogues and Synthetic Long Peptides
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Self-adjuvanting vaccines, wherein an antigenic peptide is covalently bound to an immunostimulating agent, have been shown to be promising tools for immunotherapy. Synthetic Toll-like receptor (TLR) ligands are ideal adjuvants for covalent linking to peptides or proteins. We here introduce a conjugation-ready TLR4 ligand, CRX-527, a potent powerful lipid A analogue, in the generation of novel conjugate-vaccine modalities. Effective chemistry has been developed for the synthesis of the conjugation-ready ligand as well as the connection of it to the peptide antigen. Different linker systems and connection modes to a model peptide were explored, and in vitro evaluation of the conjugates showed them to be powerful immune-activating agents, significantly more effective than the separate components. Mounting the CRX-527 ligand at the N-terminus of the model peptide antigen delivered a vaccine modality that proved to be potent in activation of dendritic cells, in facilitating antigen presentation, and in initiating specific CD8+ T-cell-mediated killing of antigen-loaded target cells in vivo. Synthetic TLR4 ligands thus show great promise in potentiating the conjugate vaccine platform for application in cancer vaccination.
- Reintjens, Niels R. M.,Tondini, Elena,De Jong, Ana R.,Meeuwenoord, Nico J.,Chiodo, Fabrizio,Peterse, Evert,Overkleeft, Herman S.,Filippov, Dmitri V.,Van Der Marel, Gijsbert A.,Ossendorp, Ferry,Codée, Jeroen D. C.
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supporting information
p. 11691 - 11706
(2020/11/26)
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- Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide
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BRD4 has emerged as an attractive target for anticancer therapy. However, BRD4 inhibitors treatment leads to BRD4 protein accumulation, together with the reversible nature of inhibitors binding to BRD4, which may limit the efficacy of BRD4 inhibitors. To address these problems, a protein degradation strategy based on the proteolysis targeting chimera (PROTAC) technology has been developed to target BRD4 recently. Herein, we present our design, synthesis and biological evaluation of a new class of PROTAC BRD4 degraders, which were based on a potent dihydroquinazolinone-based BRD4 inhibitor compound 6 and lenalidomide/pomalidomide as ligand for E3 ligase cereblon. Gratifyingly, several compounds showed excellent inhibitory activity against BRD4, and high anti-proliferative potency against human monocyte lymphoma cell line THP-1. Especially, compound 21 (BRD4 BD1, IC50 = 41.8 nM) achieved a submicromolar IC50 value of 0.81 μM in inhibiting the growth of THP-1 cell line, and was 4 times more potent than compound 6. Moreover, the mechanism study established that 21 could effectively induce the degradation of BRD4 protein and suppression of c-Myc. All of these results suggested that 21 was an efficacious BRD4 degrader for further investigation.
- Zhang, Fangqing,Wu, Zhenwei,Chen, Pan,Zhang, Jian,Wang, Tao,Zhou, Jinpei,Zhang, Huibin
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- Development of small-molecule BRD4 degraders based on pyrrolopyridone derivative
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Bromodomain-containing protein 4 (BRD4) plays a crucial role in the epigenetic regulation of gene transcription and some BRD4 inhibitors have been advanced to clinical trials. Nevertheless, the clinical application of BRD4 inhibitors could be limited by drug resistance. As an alternative strategy, the emerging Proteolysis Targeting Chimeras (PROTACs) technology has the potential to overcome the drug resistance of traditional small-molecule drugs. Based on PROTACs approaches, several BRD4 degraders were developed and have been proved to degrade BRD4 protein and inhibit tumor growth. Herein, we present the design, synthesis, and biological evaluation of pyrrolopyridone derivative-based BRD4 degraders. Four synthesized compounds displayed comparative potence against BRD4 BD1 with IC50 at low nanomolar concentrations. Anti-proliferative activity of 32a against BxPC3 cell line (IC50 = 0.165 μM) was improved by about 7-fold as compared to the BRD4 inhibitor ABBV-075. Furthermore, degrader 32a potently induced the degradation of BRD4 and inhibited the expression of c-Myc in BxPC3 cell line in a time-dependent manner. The exploration of intracellular antitumor mechanism showed 32a induced cell cycle arrest and apoptosis effectively. All the results demonstrated that compound 32a could be considered as a potential BRD4 degrader for further investigation.
- Chen, Pan,Wang, Lixun,Wang, Tao,Xu, Changliang,Zhang, Huibin,Zhang, Jian,Zheng, Peiyuan,Zhou, Jinpei,Zhu, Peiyu
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- Combretastatin A4-camptothecin micelles as combination therapy for effective anticancer activity
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Cancer is a major worldwide health problem, for which chemotherapy is a common treatment option. However drug toxicity and the development of resistance to chemotherapy are two main challenges associated with the traditional anticancer drugs. Combined pharmacological therapy based on different mechanisms might be an effective strategy in cancer treatment, and could exhibit a synergistic therapeutic efficacy. Herein, we aim to combine combretastatin A4 (CA4) and camptothecin (Cpt) chemically into a codrug through two hydrophilic linkers utilizing click chemistry to improve their water solubility and anticancer activity. The synthesized amphiphilic structure could self-assemble into a micelle structure as confirmed by atomic force microscopy (AFM) and dynamic light scattering (DLS), which showed a high stability and improved water solubility at pH 7.4, with a low critical micelle concentration (CMC) value of 0.9 mM. Moreover, in vitro hydrolysis was observed upon incubation of the hybrid compound with an esterase enzyme, which suggested a complete disassembly into the starting active drugs. Finally, cytotoxicity studies on HeLa cancer cells showed that the codrug demonstrated an enhanced (five fold) cytotoxicity as compared with the free drugs. In addition the combination index (CI) was 1, which suggests a synergistic activity for the codrug. Moreover, the tested concentrations of the codrug were not significantly cytotoxic to a noncancerous fibroblast cell line. The imaging of HeLa cells treated with FITC-loaded micelles showed a rapid internalization. In conclusion, the codrug of CA4 and Cpt might be a potential novel anticancer drug as it demonstrated a synergistic cytotoxic activity that might spare noncancerous cells.
- Assali, Mohyeddin,Kittana, Naim,Qasem, Sahar Alhaj,Adas, Raghad,Saleh, Doaa,Arar, Asala,Zohud, Osayd
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p. 1055 - 1061
(2019/01/18)
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- PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
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The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
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Page/Page column 100; 107
(2019/11/12)
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- Solid-phase synthesis of a novel phalloidin analog with on-bead and off-bead actin-binding activity
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Specific effectors of actin polymerization have found use as dynamic probes of cellular morphology that may be used to gauge cellular response to stimuli and drugs. Of various natural products that target actin, phalloidin is one of the most potent and selective inhibitors of actin depolymerization. Phalloidin and related members of the phallotoxin family are macrocyclic heptapeptides bearing a characteristic and rigidifying transannular tryptathionine bridge. Here we describe a solid-phase synthesis of a new phalloidin analog as a prototype for library development with the potential for on- and off-bead screening. To validate our method, we labelled the phalloidin derivative with a fluorescent dye which stained actin in CHO cells. Furthermore, a bioassay was developed allowing actin polymerization on beads carrying a phalloidin derivative.
- Blanc, Antoine,Todorovic, Mihajlo,Perrin, David M.
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supporting information
p. 385 - 388
(2019/01/09)
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- FLUOROHYDROXYPROLINE DERIVATIVES USEFUL IN THE PREPARATION OF PROTEOLYSIS TARGETED CHIMERAS
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There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, and to their utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for their preparation thereof, and use in medicine. There is particularly provided novel small molecule E3 ubiquitin ligase protein binding inhibitorcompounds based on a fluorohydroxyproline scaffold, to their utility as ligands in synthesizing novel PROTACs, and to synthetic methods therefor.
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Page/Page column 98; 99
(2018/04/14)
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- DERIVATIVES OF 1-[(CYCLOPENTYL OR 2-PYRROLIDINYL)CARBONYLAMINOMETHYL]-4-(1,3-THIAZOL-5-YL) BENZENE WHICH ARE USEFUL FOR THE TREATMENT OF PROLIFERATIVE, AUTOIMMUNE OR INFLAMMATORY DISEASES
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There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, having utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for the preparation thereof, and use in medicine. There is particularly provided PROTACs which bind to a protein within the bromo- and Extra-terminal (BET) family of proteins, and especially to PROTACs including novel small molecule E3 ubiquitin ligase protein binding ligand compounds which selectively induce degradation of the BRD4 protein within the bromodomain of the BET family of proteins.
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Page/Page column 83
(2016/10/24)
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- Covalent Protein Labeling by Enzymatic Phosphocholination
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We present a new protein labeling method based on the covalent enzymatic phosphocholination of a specific octapeptide amino acid sequence in intact proteins. The bacterial enzyme AnkX from Legionella pneumophila has been established to transfer functional phosphocholine moieties from synthetically produced CDP-choline derivatives to N-termini, C-termini, and internal loop regions in proteins of interest. Furthermore, the covalent modification can be hydrolytically removed by the action of the Legionella enzyme Lem3. Only a short peptide sequence (eight amino acids) is required for efficient protein labeling and a small linker group (PEG-phosphocholine) is introduced to attach the conjugated cargo.
- Heller, Katharina,Ochtrop, Philipp,Albers, Michael F.,Zauner, Florian B.,Itzen, Aymelt,Hedberg, Christian
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supporting information
p. 10327 - 10330
(2015/09/01)
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- A convergent synthetic platform for single-nanoparticle combination cancer therapy: Ratiometric loading and controlled release of cisplatin, doxorubicin, and camptothecin
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The synthesis of polymer therapeutics capable of controlled loading and synchronized release of multiple therapeutic agents remains a formidable challenge in drug delivery and synthetic polymer chemistry. Herein, we report the synthesis of polymer nanopar
- Liao, Longyan,Liu, Jenny,Dreaden, Erik C.,Morton, Stephen W.,Shopsowitz, Kevin E.,Hammond, Paula T.,Johnson, Jeremiah A.
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supporting information
p. 5896 - 5899
(2014/05/20)
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- DRUG DELIVERY POLYMER AND USES THEREOF
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Described herein are platinum-based brush-arm star polymers (Pt-BASPs), or a pharmaceutical composition thereof, for delivery of platinum-based agents, such as cisplatin. Also provided are methods and kits involving the Pt-BASPs, or a pharmaceutical compo
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Paragraph 0275-0276
(2014/10/29)
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- Copper-catalyzed azide-alkyne cycloaddition in the synthesis of polydiacetylene: "click glycoliposome" as biosensors for the specific detection of lectins
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Supramolecular self-assembly of conjugated diacetylenic amphiphile-tethered ligands photopolymerize to afford polydiacetylene (PDA) functional liposomes. Upon specific interaction with a variety of biological analytes in aqueous solution, PDA exhibits rapid colorimetric transitions. The PDA nanoassemblies, which are excellent membrane mimics, include an ene-yne polymeric reporter responsible for the chromatic transitions and the molecular recognition elements that are responsible for selective and specific binding to the biological target. A bottleneck in the fabrication of these colorimetric biosensors is the preparation of the diacetylenic monomer embedded with the recognition element of choice. In the present work, we make use of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as key step in the preparation of sugar-coated liposome biosensors. The regioselective click ligation of the triacetylenic N-(2-propynyl)pentacosa-10,12-diynamide (NPPCDAM) with a variety of mannose-and lactose-tethered azides afforded chemo-and regioselectively the corresponding 1,2,3-triazole. The obtained diacetylenic monomers were incorporated efficiently into vesicles to afford functional mannose-and lactose-coated glycoliposomes. The obtained PDA-based click glycoliposomes have been characterized by using transmission electronic microscopy (TEM), dynamic light scattering (DLS), and UV/Vis spectroscopy. The efficiency of the reported approach was demonstrated by the rapid optimization of the hydrophilic spacer between the lipidic matrix and the mannose head group for the colorimetric detection of Concavalina A.
- Leal, Manuel Pernia,Assali, Mohyeddin,Fernandez, Inmaculada,Khiar, Noureddine
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scheme or table
p. 1828 - 1836
(2011/03/22)
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- Biomimetic screening of class-B G protein-coupled receptors
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The 41-amino acid peptide corticotropin releasing factor (CRF) is a major modulator of the mammalian stress response. Upon stressful stimuli, it binds to the corticotropin releasing factor receptor 1 (CRF1R), a typical member of the class-B G-protein-coupled receptors (GPCRs) and a prime target in the treatment of mood disorders. To chemically probe the molecular interaction of CRF with the transmembrane domain of its cognate receptor, we developed a high-throughput conjugation approach that mimics the natural activation mechanism of class-B GPCRs. An acetylene-tagged peptide library was synthesized and conjugated to an azide-modified high-affinity carrier peptide derived from the CRF C-terminus using copper-catalyzed dipolar cycloaddition. The resulting conjugates reconstituted potent agonists and were tested in situ for activation of the CRF1 receptor in a cell-based assay. By use of this approach we (i) defined the minimal sequence motif that is required for full receptor activation, (ii) identified the critical functional groups and structure-activity relationships, (iii) developed an optimized, highly modified peptide probe with high potency (EC50 = 4 nM) that is specific for the activation domain of the receptor, and (iv) probed the behavioral role of CRF receptors in living mice. The membrane recruitment by a high-affinity carrier enhanced the potency of the tethered peptides by >4 orders of magnitude and thus allowed the testing of very weak initial fragments that otherwise would have been inactive on their own. As no chromatography purification of the test peptides was necessary, a substantial increase in screening throughput was achieved. Importantly, the peptide conjugates can be used to probe the endogenous receptor in its native environment in vivo.
- Devigny, Christian,Perez-Balderas, Francisco,Hoogeland, Bastiaan,Cuboni, Serena,Wachtel, Rudolf,Mauch, Christoph P.,Webb, Katharine J.,Deussing, Jan M.,Hausch, Felix
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supporting information; experimental part
p. 8927 - 8933
(2011/08/04)
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- Design, synthesis and biological evaluation of nuclear receptor-degradation inducers
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Compounds that regulate the function(s) of nuclear receptors (NRs) are useful for biological studies and as candidate therapeutic agents. Most such compounds are agonists or antagonists. On the other hand, we have developed specific protein degradation in
- Itoh, Yukihiro,Kitaguchi, Risa,Ishikawa, Minoru,Naito, Mikihiko,Hashimoto, Yuichi
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experimental part
p. 6768 - 6778
(2012/01/13)
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- Small molecule microarray-facilitated screening of affinity-based probes (AfBPs) for γ-secretase
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A small molecule microarray (SMM) platform is developed herein, which enables high-throughput discovery of affinity-based probes (AfBPs) against γ-secretase.
- Shi, Haibin,Liu, Kai,Xu, Ashley,Yao, Shao Q.
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supporting information; experimental part
p. 5030 - 5032
(2010/01/06)
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- Insulin Derivatives Conjugated with Structurally Well Defined Branched Polymers
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Insulin conjugated with structurally well defined, bifurcated and trifurcated polymers can be use by pulmonary delivery for systemic absorption through the lungs to reduce or eliminate the need for administering other insulins by injection.
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- Functional determinants of a synthetic vesicle fusion system
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Selective membrane mergers may be driven by small-molecule recognition between synthetic surface-displayed fusogens which bear vancomycin glycopeptide and its native binding target, D-Ala-D-Ala dipeptide. These recognition motifs are membrane anchored by
- Gong, Yun,Ma, Mingming,Luo, Yumei,Bong, Dennis
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p. 6196 - 6205
(2008/12/20)
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- Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics
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We have developed a heterobifunctional all-small molecule PROTAC (PROteolysis TArgeting Chimera) capable of inducing proteasomal degradation of the androgen receptor. This cell permeable PROTAC consists of a non-steroidal androgen receptor ligand (SARM) and the MDM2 ligand known as nutlin, connected by a PEG-based linker. The SARM-nutlin PROTAC recruits the androgen receptor to MDM2, which functions as an E3 ubiquitin ligase. This leads to the ubiquitination of the androgen receptor, and its subsequent degradation by the proteasome. Upon treatment of HeLa cells with 10 μM PROTAC for 7 h, we were able to observe a decrease in androgen receptor levels. This degradation is proteasome dependent, as it is mitigated in cells pre-treated with 10 μM epoxomicin, a specific proteasome inhibitor. These results have implications for the potential study and treatment of various cancers with increased androgen receptor levels.
- Schneekloth, Ashley R.,Pucheault, Mathieu,Tae, Hyun Seop,Crews, Craig M.
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experimental part
p. 5904 - 5908
(2009/06/25)
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- DERIVATIVES OF INSULINOTROPIC AGENTS CONJUGATED WITH STRUCTURALLY WELL DEFINED BRANCHED POLYMERS
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Novel GLP-1 conjugated with structurally well defined polymers and their therapeutically use.
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Page/Page column 84
(2008/06/13)
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- INSULIN DERIVATIVES CONJUGATED WITH STRUCTURALLY WELL DEFINED BRANCHED POLYMERS
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Insulin conjugated with structurally well defined, bifurcated and trifurcated polymers can be use by pulmonary delivery for systemic absorption through the lungs to reduce or eliminate the need for administering other insulins by injection.
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Page/Page column 59
(2008/06/13)
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- Highly sensitive detection of GG mismatched DNA by surfaces immobilized naphthyridine dimer through poly(ethylene oxide) linkers
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Naphthyridine dimer is a unique molecule that strongly, and selectively, binds to the guanine-guanine mismatch in duplex DNA. We have synthesized naphthyridine dimers possessing a different length of poly(ethylene oxide) (PEO) linker, and immobilized them
- Nakatani, Kazuhiko,Kobori, Akio,Kumasawa, Hiroyuki,Saito, Isao
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p. 1105 - 1108
(2007/10/03)
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- Synthesis of a polymerizable metal-ion-chelating lipid for fluid bilayers
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Hydrated lipid structures, such as liposomes, that display tethered metal-ion-chelating groups have proven useful in peptide and protein binding, as well as 2D protein crystallization through molecular recognition of accessible histidine sites in proteins and peptides. Polymerizable metal-ion-chelating lipids bearing a reactive diacetylene group have been described. These interesting compounds can be polymerized in the solid-analogous phase. Here we describe the design of the first polymerizable metal-ion-chelating lipid that can be used in the fluid, i.e., liquid analogous, phase of lipid bilayers. The synthesis of 1-palmitoyl-2-[8-[(E,E)-2′,4′-hexadienoyloxy] octanoyl]-sn-glycero-3-N-[11-[N′,N′bis- [carboxymethyl]imino]-3,6,9-trioxaundecanoyl] phosphatidylethanolamine (1) is described. The chelator moiety, iminodiacetate (IDA), was linked to the polymerizable phosphatidylethanolamine (PE) with a terminal 2,4-hexadienoyl (sorbyl) group through an oligo(ethylene glycol)-based spacer. Lipid 1-Cu complex is designed to be combined with the corresponding polymerizable matrix lipids (bis-SorbPC) to form functionalized liposomes that can be stabilized by various polymerization methods.
- Sang Won Jeong,O'Brien
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p. 4799 - 4802
(2007/10/03)
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- Spacer molecules in peptide sequences: Incorporation into analogues of atrial natriuretic factor
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In the present study, 10 modified human atrial natriuretic factor (hANF) analogues were designed using solid phase synthesis. This was carried out by replacing 'alkyl or glycol' spacer with octapeptide sequence within die cyclic portion of hANF in each annlogue synthesised. The unnatural amino acid spacers (1b) and (2d) have been synthesised using solution chemistry. The latter spacers were successfully incorporated into the peptide structure, using solid phase synthesis assembly. Amongst the ten analogues, thus prepared, two in which the alkyl spacer was used to substitute amino acid residues Gly15 to Gly21 and Arg14 to Leu21 to give 4a and 4b, successively. In the purification process of the latter analogues (4a, 4b), problems of their severe solubility were encountered. The eight glycol-spaced analogues (5a-5h) were successfully synthesised and purified using HPLC. The structure of (5a-5h) was confirmed by the presence of mass ion peaks in the atom bombardment mass spectroscopy (FAB MS) and by NMR. The latter analogues were tested, in vivo, for their ability to bind to specific hANF receptors, as agonists or antagonists. The biological results have showed that none of these analogues (5a-5h) were active.
- Boumrah, Derradji,Campbell, Malcolm M.,Fenner, Simon,Kinsman, Richard G.
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p. 6977 - 6992
(2007/10/03)
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- Rational design of multivalent glycoconjugate ligands. Synthesis of libraries of conformationally flexible rotamers of poly-N-linked lactosyl glycines
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A reiterative and convergent oligo(N-substituted glycine) strategy is used to construct combinatorial structures of conformationally flexible multivalent N-linked lactose-containing glycopeptoids having triethylene glycol spacers between the sugar residues and the peptoid backbones.
- Roy, Rene,Saha, Uttam K.
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p. 201 - 202
(2007/10/03)
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- Spacer molecules in peptide sequences: Incorporation into analogues of atrial natriuretic factor
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The spacer reagents FmocHN(CH2CH2CH2)3CH 2COOPfp (1b) and FmocHN(CH2CH2O) 3CH2COOPfp (2d) have been prepared and used to substitute for tetra-residue sequences in the cyclic portion of Atrial Natriuretic Factor (ANF) by solid phase peptide assembly.
- Boumrah, Deradji,Campbell, Malcolm M.,Fenner, Simon,Kinsman, Richard G.
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p. 7735 - 7738
(2007/10/02)
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