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https://www.readbyqxmd.com/read/29223096/discovery-of-aliphatic-chain-hydroxamates-containing-indole-derivatives-with-potent-class-i-histone-deacetylase-inhibitory-activities
#1
Shi-Wei Chao, Liang-Chieh Chen, Chia-Chun Yu, Chang-Yi Liu, Tony Eight Lin, Jih-Hwa Guh, Chen-Yu Wang, Chun-Yung Chen, Kai-Cheng Hsu, Wei-Jan Huang
Histone deacetylase (HDAC) is a validated drug target for various diseases. This study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor used to treat cutaneous T-cell lymphoma (CTCL). The structure activity relationship of the resulting compounds that inhibited HDAC was disclosed as well. Some compounds exhibited much stronger inhibitory activities than SAHA. We identified two meta-series compounds 6j and 6k with a two-carbon linker had IC50 values of 3.9 and 4.5 nM for HDAC1, respectively...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29222836/biochemical-and-structural-insights-into-a-thermostable-cellobiohydrolase-from-myceliophthora-thermophila
#2
Marco Antonio Seiki Kadowaki, Paula Higasi, Mariana Ortiz de Godoy, Rolf A Prade, Igor Polikarpov
Cellobiohydrolases hydrolyze cellulose, a linear polymer with glucose monomers linked exclusively by β-1,4 glycosidic linkages. The widespread hydrogen bonding network tethers individual cellulose polymers forming crystalline cellulose, which prevent the access of hydrolytic enzymes and water molecules. The most abundant enzyme secreted by Myceliophthora thermophila M77 in response to the presence of biomass is the cellobiohydrolase MtCel7A, which is composed by a GH7-catalytic domain (CD), a linker and a CBM1-type carbohydrate binding module...
December 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29222485/redox-switchable-breathing-behavior-in-tetrathiafulvalene-based-metal-organic-frameworks
#3
Jian Su, Shuai Yuan, Hai-Ying Wang, Lan Huang, Jing-Yuan Ge, Elizabeth Joseph, Junsheng Qin, Tahir Cagin, Jing-Lin Zuo, Hong-Cai Zhou
Metal-organic frameworks (MOFs) that respond to external stimuli such as guest molecules, temperature, or redox conditions are highly desirable. Herein, we coupled redox-switchable properties with breathing behavior induced by guest molecules in a single framework. Guided by topology, two flexible isomeric MOFs, compounds 1 and 2, with a formula of In(Me2NH2)(TTFTB), were constructed via a combination of [In(COO)4]- metal nodes and tetratopic tetrathiafulvalene-based linkers (TTFTB). The two compounds show different breathing behaviors upon the introduction of N2...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29222345/type-vi-secretion-system-sheath-inter-subunit-interactions-modulate-its-contraction
#4
Maximilian Brackmann, Jing Wang, Marek Basler
Secretion systems are essential for bacteria to survive and manipulate their environment. The bacterial type VI secretion system (T6SS) generates the force needed for protein translocation by the contraction of a long polymer called sheath. The sheath is a six-start helical assembly of interconnected VipA/VipB subunits. The mechanism of T6SS sheath contraction is unknown. Here, we show that elongating the N-terminal VipA linker or eliminating charge of a specific VipB residue abolishes sheath contraction and delivery of effectors into target cells...
December 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29222167/cytoplasmic-linker-protein-clip170-negatively-regulates-tlr4-signaling-by-targeting-the-tlr-adaptor-protein-tirap
#5
Padmaja Jakka, Bindu Bhargavi, Swapna Namani, Subathra Murugan, Gary Splitter, Girish Radhakrishnan
Cytoplasmic linker protein 170 (CLIP170) is a CAP-Gly domain-containing protein that is associated with the plus end of growing microtubules and implicated in various cellular processes, including the regulation of microtubule dynamics, cell migration, and intracellular transport. Our studies revealed a previously unrecognized property and role of CLIP170. We identified CLIP170 as one of the interacting partners of Brucella effector protein TcpB that negatively regulates TLR2 and TLR4 signaling. In this study, we demonstrate that CLIP170 interacts with the TLR2 and TLR4 adaptor protein TIRAP...
December 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29221868/influence-of-hydrogen-bond-accepting-ability-of-anions-on-the-adsorption-performance-of-ionic-liquid-surface-molecularly-imprinted-polymers
#6
Guifen Zhu, Xia Gao, Xiaolong Wang, Jianji Wang, Jing Fan
To illuminate the influence mechanism of anionic structure of ionic liquids (ILs) on the adsorption performance of surface molecularly imprinted polymers (MIPs), in this work, six newly designed MIPs were prepared on the surface of amino-poly(styrene-divinylbenzene) particles by using imidazolium ILs with the same cation [C4mim]+ but different anions (Cl, CH3SO3, PF6, BF4, C4F7O2, C4F9SO3) as template molecules, methacrylic acid as functional monomer, and ethylene dimethacrylate as cross-linker. The resulting MIP materials were characterized by IR and SEM, and the influence of hydrogen bond accepting ability of anions on the adsorption performance of the MIPs for the ILs was investigated in acetonitrile...
November 26, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29220154/set-of-multifunctional-azo-functionalized-semiconducting-cd-ii-mofs-showing-photoswitching-property-and-selective-co2-adsorption
#7
Dilip Kumar Maity, Arka Dey, Saheli Ghosh, Arijit Halder, Partha Pratim Ray, Debajyoti Ghoshal
Syntheses, structural characterizations, photoluminescence, and adsorption properties of three new azo-functionalized Cd(II)-MOFs, namely, {[Cd(azbpy)(msuc)]·2.5(H2O)}n (2), {[Cd(azbpy)(mglu)]·5(H2O)}n (3), and {[Cd1.5(azbpy)2(glu)]·(NO3)·MeOH}n (4) [where msuc2- = methylsuccinate; mglut2- = methylglutarate; glut2- = glutarate; azbpy = 4,4'-azobispyridine] have been reported. The compounds show different structures only with the variation of aliphatic dicarboxylates. The photoswitching behavior for the above-mentioned newly synthesized Cd(II)-MOFs along with one of our previously reported other azo-functionalized Cd(II)-MOF, namely, {[Cd(azbpy)(suc)]·2(H2O)}n (1), has been studied extensively...
December 8, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/29220050/a-pair-of-polymorphous-metal-organic-frameworks-based-on-an-angular-diisophthalate-linker-synthesis-characterization-and-gas-adsorption-properties
#8
Fengli Chen, Dongjie Bai, Yao Wang, Minghui He, Xiaoxia Gao, Yabing He
The combination of an angular diisophthalate ligand, 5,5'-(naphthyl-2,7-yl)diisophthalate (H4L), and copper ions under different solvothermal conditions afforded two polymorphous metal-organic frameworks (ZJNU-77 and ZJNU-78) with the same framework composition of [Cu2(L)(H2O)2], providing a platform to investigate the relationship between MOF polymorphism and gas adsorption properties. As determined by single-crystal X-ray diffraction, ZJNU-77 and ZJNU-78 exhibited three-dimensional networks crystallizing in different space groups...
December 8, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29218606/pi3k-is-a-linker-between-l-selectin-and-psgl-1-signaling-to-il-18-transcriptional-activation-at-the-promoter-level
#9
Jixian Luo
L-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are adhesion molecules which induce similar physiological events. Our previous paper showed that phosphatidylinositol 3-kinase (PI3K) played a crucial role in L-selectin- and PSGL-1-mediated F-actin redistribution and assembly during neutrophil rolling on E-selectin. However, it is not clear whether L-selectin and PSGL-1 induce other similar physiology events by PI3K. Here, we investigated the possibility of PI3K linking the signaling pathways of L-selectin and PSGL-1 to IL-18 transcription...
December 7, 2017: Inflammation
https://www.readbyqxmd.com/read/29218499/effect-of-clip3-upregulation-on-astrocyte-proliferation-and-subsequent-glial-scar-formation-in-the-rat-spinal-cord-via-stat3-pathway-after-injury
#10
Xiaoqing Chen, Cheng Chen, Jie Hao, Jiyun Zhang, Feng Zhang
Spinal cord injury (SCI) is a devastating event resulting in neuron degeneration and permanent paralysis through inflammatory cytokine overproduction and glial scar formation. Presently, the endogenous molecular mechanisms coordinating glial scar formation in the injured spinal cord remain elusive. Signal transducer and activator of transcription 3 (STAT3) is a well-known transcription factor particularly involving in cell proliferation and inflammation in the lesion site following SCI. Meanwhile, CAP-Gly domain containing linker protein 3(CLIP3), a vital cytoplasmic protein, has been confirmed to providing an optimal conduit for intracellular signal transduction and interacting with STAT3 with mass spectrometry analysis...
December 7, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29217763/improved-tumor-penetration-and-single-cell-targeting-of-antibody-drug-conjugates-increases-anticancer-efficacy-and-host-survival
#11
Cornelius Cilliers, Bruna Menezes, Ian Nessler, Jennifer Linderman, Greg Thurber
Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small molecule payload and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADC is poorly understood. Here we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, co-administration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared to T-DM1 alone...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29216761/efficient-therapeutic-protein-expression-using-retroviral-replicating-vector-with-2a-peptide-in-cancer-models
#12
Andrew Hofacre, Kader Yagiz, Daniel Mendoza, Fernando Lopez Espinoza, Anthony Munday, Cindy Burrascano, Oded Singer, Harry Gruber, Doug Jolly, Amy Lin
Toca 511, a retroviral replicating vector (RRV), uses an internal ribosomal entry site (IRES) to express an optimized yeast cytosine deaminase (yCD2), which converts 5-fluorocytosine to 5-fluorouracil. This configuration is genetically stable in both preclinical mouse models and human clinical trials. However, the use of IRES (~ 600 bp) restricts choices of therapeutic transgenes due to limits in RRV genome size. In this study, we replaced IRES with 2A peptides derived from picornaviruses with or without a GSG linker...
December 7, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29216514/modulation-of-in-vitro-phagocytic-uptake-and-immunogenicity-potential-of-modified-herceptin%C3%A2-conjugated-plga-peg-nanoparticles-for-drug-delivery
#13
Apurva Badkas, Evan Frank, Zilan Zhou, Mina Jafari, Harish Chandra, Vishnu Sriram, Joo-Youp Lee, Jagjit S Yadav
There is an increasing interest in engineered nanoparticle (NP) conjugates for targeted and controlled drug delivery. However, the practical applications of these NP delivery vehicles remain constrained because of their reactivity with the body's immune system defenses resulting in undesirable off-target effects. In this study, poly(D,L lactide-co-glycolide) (PLGA)-b-polyethylene glycol (PEG) NPs conjugated to different quantities of the commercial antibody Herceptin® meant to target HER2-positive breast cancer cells were studied for their immune cell uptake and immunogenic properties (using murine macrophages and human dendritic cells)...
December 4, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29215862/reticular-chemistry-and-the-discovery-of-a-new-family-of-rare-earth-4-8-connected-metal-organic-frameworks-with-csq-topology-based-on-re4-%C3%AE-3-%C3%AE-2-coo-8-clusters
#14
Giasemi K Angeli, Christina Sartsidou, Styliani Vlahaki, Ioannis Spanopoulos, Constantinos Tsangarakis, Andreas Kourtellaris, Emmanouel Klontzas, George E Froudakis, Anastasios J Tasiopoulos, Pantelis N Trikalitis
In recent years, the design and discovery of new MOF platforms with distinct structural features and tunable chemical composition has remarkably enhanced by applying reticular chemistry rules and the molecular building block (MBB) ap-proach. We targeted the synthesis of new RE-MOF platforms based on a rectangular shaped 4-c linker, acting as a rigid organic MBB. Accordingly, we designed and synthesized the organic ligand 1,2,4,5-tetrakis(4-carboxyphenyl)-3,6-dimethyl-benzene, H4L, in which the two methyl groups attached to the central phenyl ring, lock the four peripheral carboxyphenyl groups to an orthogonal/vertical position...
December 7, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29215671/the-role-of-structure-and-the-metal-ion-in-the-fluorescence-sensing-of-nitro-compounds-for-a-series-of-lanthanide-iii-9-10-anthracene-dicarboxylate-coordination-polymers
#15
Hong Sheng Quah, Li Ting Ng, Jagadese J Vittal
Twenty-eight lanthanide coordination polymers (CPs) containing 9,10-anthracene dicarboxylate (ADC) linkers have been synthesized and characterized. For the earlier class of lanthanides La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+ and Tb3+, the 3D pcu net was generated from dimethylformamide (DMF) while a 2D hcb net was formed using dimethylacetamide (DMA). Similarly for the later class of lanthanides, Dy3+, Ho3+, Er3+, Tm3+, Yb3+ and Lu3+, a 2D hcb net was formed when dimethylacetamide (DMA) was used. However, the formation of a crystalline product with DMF was possible only when DMSO was added together for these lanthanides, and they yielded 2D structures despite the usage of DMF...
December 7, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29215271/high-proton-conduction-in-crystalline-composites-based-on-preyssler-type-polyoxometalates-and-polymers-under-nonhumidified-or-humidified-conditions
#16
Kazuma Niinomi, Satoru Miyazawa, Mitsuhiro Hibino, Noritaka Mizuno, Sayaka Uchida
Keggin-type polyoxometalate (POM)-based compounds have long been considered as one of the environmentally friendly candidates of solid electrolytes exhibiting high proton conductivity under high relative humidity (RH >95%). However, their application has been limited by the lack of structural stability and large decrease in conductivity with a slight decrease in RH. In order to overcome these disadvantages, we report a series of crystalline composites based on Preyssler-type POMs ([Na(H2O)P5W30O110]14-, [Bi(H2O)P5W30O110]12-), which are known to show higher acidity in comparison to Keggin-type POMs, and polymers (polyethylene glycol (PEG), polyallylamine (PAA))...
December 7, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/29214842/trastuzumab-emtansine-determining-its-role-in-management-of-her2-breast-cancer
#17
Deborah B Doroshow, Patricia M LoRusso
Trastuzumab emtansine is an antibody-drug conjugate comprised of the anti-HER2 monoclonal antibody trastuzumab linked to DM1 (emtansine), a potent cytotoxic maytansinoid derivative, by a stable linker. This structure results in improved tumor-directed cytotoxicity in HER2+ breast cancer with reduced systemic toxicities, particularly the cardiac toxicities associated with single agent trastuzumab. Phase III trials have demonstrated improved progression-free and overall survival in heavily pretreated patients with advanced HER2+ breast cancer, with an acceptable toxicity profile...
December 7, 2017: Future Oncology
https://www.readbyqxmd.com/read/29214708/chemicals-on-demand-photo-induced-release-from-nano-and-microparticle-containers
#18
Ulrich S Schubert, Christoph Englert, Ivo Nischang, Cornelia Bader, Philipp Borchers, Julien Alex, Michael Proehl, Martin Hentschel, Matthias Hartlieb, Anja Traeger, Georg Pohnert, Stephanie Schubert, Michael Gottschaldt
A benzoin-derived diol linker was synthesized and used to create biocompatible polyesters, which can be fully decomposed on demand triggered by UV light. Extensive structural optimization of the linker unit was performed to enable a defined encapsulation of structurally diverse organic compounds in polymeric structures and a well-controllable polymer cleavage process. Selective tracking of release kinetics of encapsulated model compounds from the polymeric nano- and microparticle containers was enabled by confocal laser scanning microscopy as a proof-of-principle for desired applications...
December 6, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29214251/photoresponsive-spherical-nucleic-acid-spatiotemporal-control-of-the-assembly-circuit-and-intracellular-microrna-release
#19
Xiang Zhou, Hui Li, Miao He, Xue Yin, Dongbao Yao, Shiyan Xiao, Haojun Liang
Herein, we designed and prepared a photoresponsive spherical nucleic acid (SNA) conjugate by inserting a photocleavable linker into the recognition sequence of SNA which can block the reactivity of the system temporally until specific UV light (∼365 nm) is introduced. The photoresponsive SNA realizes temporal regulation of a self-assembly reaction circuit and spatial selectivity of microRNA release in a cell population, respectively.
December 7, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29213270/nanobodies-and-nanobody-based-human-heavy-chain-antibodies-as-antitumor-therapeutics
#20
REVIEW
Peter Bannas, Julia Hambach, Friedrich Koch-Nolte
Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv)...
2017: Frontiers in Immunology
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