keyword
MENU ▼
Read by QxMD icon Read
search

Drug structure

keyword
https://www.readbyqxmd.com/read/29458213/selective-targeting-and-degradation-of-doxorubicin-loaded-folate-functionalized-dna-nanocages
#1
Sofia Raniolo, Giulia Vindigni, Alessio Ottaviani, Valeria Unida, Federico Iacovelli, Antonio Manetto, Mariangela Figini, Lorenzo Stella, Alessandro Desideri, Silvia Biocca
Selective targeting is a crucial property of nanocarriers used for drug delivery in cancer therapy. We generated biotinylated octahedral DNA nanocages functionalized with folic acid through bio-orthogonal conjugation chemistry. Molecular modelling indicated that a distance of about 2.5 nm between folic acid and DNA nanocage avoids steric hindrance with the folate receptor. HeLa cells, a folate receptor positive tumour cell line, internalize folate-DNA nanocages with efficiency greater than 40 times compared to cells not expressing the folate receptors...
February 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29458130/impact-of-rna-polymerase-i-inhibitor-cx-5461-on-viral-kinase-dependent-and-independent-cytomegalovirus-replication
#2
Kristen N Westdorp, Scott S Terhune
Human cytomegalovirus (HCMV) infections cause congenital birth defects and disease in immunosuppressed individuals. Antiviral compounds can control infection yet their use is restricted due to concerns of toxicity and the emergence of drug resistant strains. We have evaluated the impact of an RNA Polymerase I (Pol I) inhibitor, CX-5461 on HCMV replication. CX-5461 inhibits Pol I-mediated ribosomal DNA transcription by binding G-quadruplex DNA structures and also activates cellular stress response pathways. The addition of CX-5461 at both early and late stages of the HCMV infection inhibited viral DNA synthesis and virus production...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458089/structural-and-biophysical-insight-into-dual-site-binding-of-the-protoberberine-alkaloid-palmatine-to-parallel-g-quadruplex-dna-using-nmr-fluorescence-and-circular-dichroism-spectroscopy
#3
Kumar Padmapriya, Ritu Barthwal
Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4 , has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by1 H and31 P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra...
February 16, 2018: Biochimie
https://www.readbyqxmd.com/read/29458023/structural-characterization-of-the-hcov-229e-fusion-core
#4
Wei Zhang, Qianqian Zheng, Mengrong Yan, Xiaobo Chen, Haitao Yang, Weihong Zhou, Zihe Rao
HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This protein is composed of an N-terminal receptor-binding domain (S1) and a C-terminal trans-membrane fusion domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2). In this study, the HRs sequences were designed and connected with a flexible linker. The recombinant fusion core protein was crystallized and its structure was solved at a resolution of 2.45 Å. Then we characterized the binding of HR1s and HR2s via both sequence alignment and structural analysis...
February 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29458018/5-chloro-n4-2-isopropylsulfonyl-phenyl-n2-2-methoxy-4-4-4-methylpiperazin-1-yl-methyl-1h-1-2-3-triazol-1-yl-phenyl-pyrimidine-2-4-diamine-wy-135-a-novel-alk-inhibitor-induces-cell-cycle-arrest-and-apoptosis-through-inhibiting-alk-and-its-downstream-pathways
#5
Mengting Han, Jiwei Shen, Lijing Wang, Yu Wang, Xin Zhai, Yao Li, Meiqiao Liu, Zengqiang Li, Daiying Zuo, Yingliang Wu
Anaplastic lymphoma kinase (ALK)-positive cancers have rising morbidity and mortality in recent years, and novel chemotherapeutic drugs with no drug resistance and high activity for treating ALK-positive cancers are needed urgently. In this study, we investigated the anti-cancer effect of 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a novel ALK inhibitor, on nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) positive cancer cell line Karpas299 and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) positive cancer cell line H2228...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29457894/small-molecule-allosteric-modulators-of-g-protein-coupled-receptors-drug-target-interactions
#6
Shaoyong Lu, Jian Zhang
G-protein-coupled receptors (GPCRs) are the largest class of signaling receptors that are most frequently targeted by therapeutic drugs. Allosteric modulators bound to GPCRs at allosteric sites provide the potential for differential selectivity and improved safety compared with traditional orthosteric ligands. The recent breakthroughs in GPCR structural biology have made structures of GPCRs from classes A, B, C, and F complexed with small-molecule allosteric modulators available. Knowledge on the detailed receptor-modulator interactions at the allosteric sites is useful for structure-based GPCR drug design of novel therapeutics...
February 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29457857/towards-structural-studies-of-self-assembled-subviral-particles-combining-cell-free-expression-with-100-khz-mas-nmr
#7
Guillaume David, Marie-Laure Fogeron, Maarten Schledorn, Roland Montserret, Uta Haselmann, Susanne Penzel, Aurelie Badillo, Lauriane Lecoq, Patrice André, Michael Nassal, Ralf Bartenschlager, Beat H Meier, Anja Böckmann
Viral membrane proteins are prime targets in the combat against infection. Still, their structure determination remains a challenge, both with respect to sample preparation, and the need for structural methods allowing analysis in a native-like lipid environment. Cell-free protein synthesis and solid-state NMR are promising approaches in this context, one with respect to its high potential of native expression of complex proteins, and the other for its ability to analyze membrane proteins in lipids. We here show that milligram amounts of the small envelope protein of the duck hepatitis B virus (DHBV) can be produced using cell-free expression, and that the protein self-assembles into subviral particles...
February 19, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29457794/recon3d-enables-a-three-dimensional-view-of-gene-variation-in-human-metabolism
#8
Elizabeth Brunk, Swagatika Sahoo, Daniel C Zielinski, Ali Altunkaya, Andreas Dräger, Nathan Mih, Francesco Gatto, Avlant Nilsson, German Andres Preciat Gonzalez, Maike Kathrin Aurich, Andreas Prlić, Anand Sastry, Anna D Danielsdottir, Almut Heinken, Alberto Noronha, Peter W Rose, Stephen K Burley, Ronan M T Fleming, Jens Nielsen, Ines Thiele, Bernhard O Palsson
Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures...
February 19, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29457755/novel-approach-for-ces1-genotyping-integrating-single-nucleotide-variants-and-structural-variation
#9
Ditte Bjerre, Henrik Berg Rasmussen
AIM: Development of a specific procedure for genotyping of CES1A1 (CES1) and CES1A2, a hybrid of CES1A1 and the pseudogene CES1P1. MATERIALS & METHODS: The number of CES1A1 and CES1A2 copies and that of CES1P1 were determined using real-time PCR. Long range PCRs followed by secondary PCRs allowed sequencing of single nucleotide variants in CES1A1 and CES1A2. Results & conlusion: A procedure consisting of two main steps was developed. Its first main step, the copy number determination, informed about presence of CES1A2 ...
February 19, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29457729/assessing-interactions-between-a-polytopic-membrane-protein-and-lipid-bilayers-using-differential-scanning-calorimetry-and-solid-state-nmr
#10
James R Banigan, Maureen Leninger, Ampon Sae Her, Nathaniel J Traaseth
It is known that the lipid composition within a cellular membrane can influence membrane protein structure and function. In this Article, we investigated how structural changes to a membrane protein upon substrate binding can impact the lipid bilayer. To carry out this study, we reconstituted the secondary active drug transporter EmrE into a variety of phospholipid bilayers varying in headgroup and chain length and carried out differential scanning calorimetry (DSC) and solid-state NMR experiments. The DSC results revealed a difference in cooperativity of the lipid phase transition for drug-free EmrE protonated at glutamic acid 14 (i...
February 19, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29457713/probing-structural-changes-among-analogous-inhibitor-bound-forms-of-hiv-1-protease-and-a-drug-resistant-mutant-in-solution-by-nuclear-magnetic-resonance
#11
Shahid N Khan, John D Persons, Janet L Paulsen, Michel Guerrero, Celia A Schiffer, Nese Kurt-Yilmaz, Rieko Ishima
In the era of state-of-the-art inhibitor design and high-resolution structural studies, detection of significant but small protein structural differences in the inhibitor-bound forms is critical to further developing the inhibitor. Here, we probed differences in HIV-1 protease (PR) conformation among darunavir and four analogous inhibitor-bound forms and compared them with a drug-resistant mutant using nuclear magnetic resonance chemical shifts. Changes in amide chemical shifts of wild-type (WT) PR among these inhibitor-bound forms, ΔCSP, were subtle but detectable and extended >10 Å from the inhibitor-binding site, asymmetrically between the two subunits of PR...
February 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29457668/the-relationships-between-depression-neuroticism-and-attitudes-nda-model-in-heroin-abusers-in-taiwan
#12
Kun-Hua Lee, Cheng-Fang Yen
BACKGROUND AND OBJECTIVES: Heroin use is a severe problem worldwide. To develop more effective treatments for heroin abusers, a comprehensive psychosocial model of heroin use should be established and examined. We created and assessed a neuroticism, depression, attitudes, and heroin addiction (NDA) model. METHODS: In this cross-sectional study, 234 patients undergoing methadone replacement treatment were recruited from psychiatric clinics. We used Structural Equation Modeling (SEM) to assess all for neuroticism, depression, and a positive outcome expectancy (POE) (attitudes)...
February 19, 2018: American Journal on Addictions
https://www.readbyqxmd.com/read/29457593/characterization-study-and-optimization-of-swelling-behavior-for-p-hema-co-eudragit-l-100-hydrogels-by-using-taguchi-method
#13
Hediye Irem Ozgunduz, Abdullah Bilal Ozturk, Hava Gizem Kandilci, Nil Acarali
The aim of this study is to produce the smart hydrogel to use insulin release for human body. p(HEMA-co-Eudragit L-100) hydrogels containing different ratios of 2-Hydroxyethyl methacrylate (HEMA) and Eudragait L-100 were synthesized by using ammonium persulfate (APS) as an initiator and ethylene glycol dimethacrylate (EGDMA) as a cross linker. The structures of hydrogels produced were characterized by using Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning electron microscope (SEM) analysis. In this way, optimum synthesis conditions were determined for p(HEMA-co-Eudragit L-100) hydrogels by using Taguchi method as an optimization method...
2018: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/29457585/training-nurses-in-a-competency-framework-to-support-adults-with-epilepsy-and-intellectual-disability-the-epaid-cluster-rct
#14
Howard Ring, James Howlett, Mark Pennington, Christopher Smith, Marcus Redley, Caroline Murphy, Roxanne Hook, Adam Platt, Nakita Gilbert, Elizabeth Jones, Joanna Kelly, Angela Pullen, Adrian Mander, Cam Donaldson, Simon Rowe, James Wason, Fiona Irvine
BACKGROUND: People with an intellectual (learning) disability (ID) and epilepsy have an increased seizure frequency, higher frequencies of multiple antiepileptic drug (AED) use and side effects, higher treatment costs, higher mortality rates and more behavioural problems than the rest of the population with epilepsy. The introduction of nurse-led care may lead to improvements in outcome for those with an ID and epilepsy; however, this has not been tested in a definitive clinical trial...
February 2018: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/29457543/greener-chemicals-for-the-future-qsar-modelling-of-the-pbt-index-using-eta-descriptors
#15
P De, K Roy
Persistent, bioaccumulative and toxic (PBT) chemicals symbolize a group of substances that are not easily degraded; instead, they accumulate in different organisms and exhibit an acute or chronic toxicity. The limited empirical data on PBT chemicals, the high cost of testing together with the regulatory constraints and the international push for reduced animal testing motivate a greater reliance on predictive computational methods like quantitative structure-activity relationship (QSAR) models in PBT assessment...
April 2018: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/29457450/graphdiyne-nanosheet-based-drug-delivery-platform-for-photothermal-chemo-therapy-combination-treatment-of-cancer
#16
Jun Jin, Mengyu Guo, Jiaming Liu, Jing Liu, Huige Zhou, Jiayang Li, Liming Wang, Huibiao Liu, Yuliang Li, Yuliang Zhao, Chunying Chen
Nowadays, two-dimensional (2D) materials have attracted extensive attention as cancer drug delivery platforms, owing to their unparalleled physicochemical properties and superior specific surface area. Graphdiyne (GDY) is a novel 2D carbon material. Compared to graphene, GDY not only has benzene rings composed of sp2 hybridized carbon atoms, but also has acetylene units composed of sp hybridized carbon atoms, therefore it possesses multiple conjugated electronic structures. Herein, we used doxorubicin (DOX) as a model drug to develop a GDY nanosheet-based drug delivery platform for a photothermal/chemo-therapy combination in living mice...
February 19, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29457449/catalytically-active-single-chain-polymeric-nanoparticles-exploring-their-functions-in-complex-biological-media
#17
Yiliu Liu, Silvia Pujals, Patrick J M Stals, Thomas Pauloehrl, Stanislav I Presolski, E W Meijer, Lorenzo Albertazzi, Anja R A Palmans
Dynamic single-chain polymeric nanoparticles (SCPNs) are intriguing, bioinspired architectures that result from the collapse or folding of an individual polymer chain into a nanometer-sized particle. Here we present a detailed biophysical study on the behavior of dynamic SCPNs in living cells and an evaluation of their catalytic functionality in such a complex medium. We first developed a number of delivery strategies that allowed the selective localization of SCPNs in different cellular compartments. Live/dead tests showed that the SCPNs were not toxic to cells while spectral imaging revealed that SCPNs provide a structural shielding and reduced the influence from the outer biological media...
February 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29457278/zwitterionic-nanocages-overcome-the-efficacy-loss-of-biologic-drugs
#18
Bowen Li, Zhefan Yuan, Peng Zhang, Andrew Sinclair, Priyesh Jain, Kan Wu, Caroline Tsao, Jingyi Xie, Hsiang-Chieh Hung, Xiaojie Lin, Tao Bai, Shaoyi Jiang
For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself...
February 19, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29457204/prevention-and-management-of-childhood-obesity
#19
Aashima Dabas, Anju Seth
Childhood obesity has been recognized as a global pandemic. Preventive strategies have proven to be the most effective public health intervention in curbing this pandemic. A multi-component approach involving dietary modification and advocacy for a healthy lifestyle comprising of regular physical activity, minimizing screen time and behavioral interventions have been found beneficial in preventing obesity. A life-cycle approach has been recommended where preventive interventions go as far back as affecting maternal, fetal and early childhood nutrition and lifestyle...
February 19, 2018: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/29456793/synthesis-of-novel-tetrahydroisoquinoline-cxcr4-antagonists-with-rigidified-side-chains
#20
Edgars Jecs, Eric J Miller, Robert J Wilson, Huy H Nguyen, Yesim A Tahirovic, Brook M Katzman, Valarie M Truax, Michelle B Kim, Katie M Kuo, Tao Wang, Chi S Sum, Mary E Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
A structure-activity relationship study of potent TIQ15-derived CXCR4 antagonists is reported. In this investigation, the TIQ15 side-chain was constrained to improve its drug properties. The cyclohexylamino congener 15a was found to be a potent CXCR4 inhibitor (IC50 = 33 nM in CXCL12-mediated Ca2+ flux) with enhanced stability in liver microsomes and reduced inhibition of CYP450 (2D6). The improved CXCR4 antagonist 15a has potential therapeutic application as a single agent or combinatory anticancer therapy...
February 8, 2018: ACS Medicinal Chemistry Letters
keyword
keyword
44759
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"