scholarly journals (−)-Homosalinosporamide A and Its Mode of Proteasome Inhibition: An X-ray Crystallographic Study

Marine Drugs ◽  
2018 ◽  
Vol 16 (7) ◽  
pp. 240 ◽  
Author(s):  
Michael Groll ◽  
Henry Nguyen ◽  
Sreekumar Vellalath ◽  
Daniel Romo
Keyword(s):  
Natural Product ◽  
Active Site ◽  
Late Stage ◽  
Enzyme Assay ◽  
Proteasome Inhibition ◽  
Fine Tuning ◽  
Synthetic Approach ◽  
X Ray ◽  
Salinosporamide A ◽  
Crystallographic Study

Upon acylation of the proteasome by the β-lactone inhibitor salinosporamide A (SalA), tetrahydrofuran formation occurs by intramolecular alkylation of the incipient alkoxide onto the choroethyl sidechain and irreversibly blocks the active site. Our previously described synthetic approach to SalA, utilizing a bioinspired, late-stage, aldol-β-lactonization strategy to construct the bicyclic β-lactone core, enabled synthesis of (–)-homosalinosporamide A (homoSalA). This homolog was targeted to determine whether an intramolecular tetrahydropyran is formed in a similar manner to SalA. Herein, we report the X-ray structure of the yeast 20S proteasome:homoSalA-complex which reveals that tetrahydropyran ring formation does not occur despite comparable potency at the chymotrypsin-like active site in a luminogenic enzyme assay. Thus, the natural product derivative homoSalA blocks the proteasome by a covalent reversible mode of action, opening the door for further fine-tuning of proteasome inhibition.

Human α-Thrombin Inhibition by the Active Site Titrant Nα-(N,N-dimethylcarbamoyl)-α-azalysine p-nitrophenyl ester: A Comparative Kinetic and X-ray Crystallographic Study

1996 ◽  
Vol 258 (5) ◽  
pp. 851-859 ◽  
Author(s):  
Marco Nardini ◽  
Alessandra Pesce ◽  
Menico Rizzi ◽  
Elena Casale ◽  
Raffaella Ferraccioli ◽  
...  
Keyword(s):  
Active Site ◽  
X Ray ◽  
Thrombin Inhibition ◽  
Crystallographic Study ◽  
Nitrophenyl Ester

scholarly journals Arginine 54 in the active site of escherichia coli aspartate transcarbamoylase is critical for catalysis: A site-specific mutagenesis, NMR, and X-ray crystallographic study

1992 ◽  
Vol 1 (11) ◽  
pp. 1435-1446 ◽  
Author(s):  
Jeffrey W. Stebbins ◽  
Diane E. Robertson ◽  
Mary F. Roberts ◽  
Raymond C. Stevens ◽  
William N. Lipscomb ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Active Site ◽  
Aspartate Transcarbamoylase ◽  
Site Specific ◽  
X Ray ◽  
Crystallographic Study ◽  
A Site

Convergent Total Synthesis of Principinol D, a Rearranged Kaurane Diterpenoid

2019 ◽  
Author(s):  
Timothy Newhouse ◽  
Aneta Turlik ◽  
Yifeng Chen ◽  
Anthony Scruse
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Late Stage ◽  
Membered Ring ◽  
Entry Point ◽  
Ketone Reduction ◽  
Coupling Approach

<div> <p>The total synthesis of principinol D, a rearranged kaurane diterpenoid, is reported. This grayanane natural product is constructed via a convergent fragment coupling approach, wherein the central 7-membered ring is synthesized at a late stage. The bicyclo[3.2.1]octane fragment is accessed by a Ni-catalyzed α-vinylation reaction. Strategic reductions include a diastereoselective SmI<sub>2</sub>-mediated ketone reduction with PhSH and a new protocol for selective ester reduction in the presence of ketones. The convergent strategy reported herein may be an entry point to the larger class of kaurane diterpenoids.</p> </div>

X-ray Crystallographic Study of Alkylammonium Anthracene-9-carboxylates as a Model for Fibrous Structure of Binary Anthracene Salt Gels

2004 ◽  
Vol 69 (6) ◽  
pp. 1292-1300 ◽  
Author(s):  
Tahahiro Tani ◽  
Kazuki Sada ◽  
Masatsugu Ayabe ◽  
Yuya Iwashita ◽  
Takanori Kishida ◽  
...  
Keyword(s):  
Alkyl Chain ◽  
Columnar Structure ◽  
Hydrogen Bond Network ◽  
One Dimensional ◽  
X Ray ◽  
Crystallographic Study ◽  
Alkylammonium Salts ◽  
Bond Network ◽  
Fibrous Assemblies ◽  
Long Alkyl Chain

Crystal structure of hexylammonium anthracene-9-carboxylate was investigated. The salt was arranged by a one-dimensional hydrogen bond network to form a columnar structure in the crystalline state. This columnar structure should be the model of fibrous assemblies in the organogels of anthracene-9-carboxylate alkylammonium salts having a long alkyl chain.

scholarly journals Effect of tungsten disulfide nanotubes on crystallization of polylactide under uniaxial deformation and annealing

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Fausta Loffredo ◽  
Loredana Tammaro ◽  
Tiziana Di Luccio ◽  
Carmela Borriello ◽  
Fulvia Villani ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Structural Evolution ◽  
Tungsten Disulfide ◽  
Fine Tuning ◽  
Nanocomposite Films ◽  
Uniaxial Deformation ◽  
Scanning Calorimetry ◽  
X Ray ◽  
X Ray Scattering

AbstractTungsten disulfide (WS2) nanotubes (NTs) are examined here as a filler for polylactide (PLA) for their ability to accelerate PLA crystallization and for their promising biocompatibility in relevant to biomedical applications of PLA-WS2 nanocomposites. In this work, we have studied the structural and thermal properties of PLA-WS2 nanocomposite films varying the concentration of WS2 NTs from 0 (neat PLA) to 0.6 wt%. The films were uniaxially drawn at 90 °C and annealed at the same temperature for 3 and 10 min. Using wide angle x-ray scattering, Raman spectroscopy and differential scanning calorimetry, we probed the effects of WS2 NT addition on the structure of the PLA films at various stages of processing (unstretched, stretching, annealing). We found that 0.6 wt% of WS2 induces the same level of crystallinity in as stretched PLA-WS2 as annealing in neat PLA for 10 min. These data provide useful insights into the role of WS2 NTs on the structural evolution of PLA-WS2 composites under uniaxial deformation, and extend their applicability to situations where fine tuning of PLA crystallinity is desirable.

scholarly journals X-ray Crystallographic Study of the Erabutoxins and of a Diiodo Derivative

1971 ◽  
Vol 246 (13) ◽  
pp. 4366-4368 ◽  
Author(s):  
Barbara W. Low ◽  
Reginald Potter ◽  
Richard B. Jackson ◽  
Nobuo Tamiya ◽  
Showbu Sato
Keyword(s):  
X Ray ◽  
Crystallographic Study

scholarly journals COVID-19 diagnosis from chest X-ray images using transfer learning: Enhanced performance by debiasing dataloader

2021 ◽  
Vol 29 (1) ◽  
pp. 19-36
Author(s):  
Çağín Polat ◽  
Onur Karaman ◽  
Ceren Karaman ◽  
Güney Korkmaz ◽  
Mehmet Can Balcı ◽  
...  
Keyword(s):  
Transfer Learning ◽  
Critical Time ◽  
Image Data ◽  
Mapping Method ◽  
Fine Tuning ◽  
Learning Stage ◽  
X Ray ◽  
Testing Dataset ◽  
X Ray Imaging ◽  
Chest X Ray

BACKGROUND: Chest X-ray imaging has been proved as a powerful diagnostic method to detect and diagnose COVID-19 cases due to its easy accessibility, lower cost and rapid imaging time. OBJECTIVE: This study aims to improve efficacy of screening COVID-19 infected patients using chest X-ray images with the help of a developed deep convolutional neural network model (CNN) entitled nCoV-NET. METHODS: To train and to evaluate the performance of the developed model, three datasets were collected from resources of “ChestX-ray14”, “COVID-19 image data collection”, and “Chest X-ray collection from Indiana University,” respectively. Overall, 299 COVID-19 pneumonia cases and 1,522 non-COVID 19 cases are involved in this study. To overcome the probable bias due to the unbalanced cases in two classes of the datasets, ResNet, DenseNet, and VGG architectures were re-trained in the fine-tuning stage of the process to distinguish COVID-19 classes using a transfer learning method. Lastly, the optimized final nCoV-NET model was applied to the testing dataset to verify the performance of the proposed model. RESULTS: Although the performance parameters of all re-trained architectures were determined close to each other, the final nCOV-NET model optimized by using DenseNet-161 architecture in the transfer learning stage exhibits the highest performance for classification of COVID-19 cases with the accuracy of 97.1 %. The Activation Mapping method was used to create activation maps that highlights the crucial areas of the radiograph to improve causality and intelligibility. CONCLUSION: This study demonstrated that the proposed CNN model called nCoV-NET can be utilized for reliably detecting COVID-19 cases using chest X-ray images to accelerate the triaging and save critical time for disease control as well as assisting the radiologist to validate their initial diagnosis.

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