scholarly journals New leads for fragment-based design of rhenium/technetium radiopharmaceutical agents

IUCrJ ◽  
2017 ◽  
Vol 4 (3) ◽  
pp. 283-290 ◽  
Author(s):  
Alice Brink ◽  
John R. Helliwell
Keyword(s):  
Binding Sites ◽  
Target Identification ◽  
Peak Height ◽  
Wavelength Tuning ◽  
Amino Acid Residues ◽  
X Ray ◽  
The Core ◽  
Height Increase ◽  
Radiopharmaceutical Agents ◽  
State Of Art

Multiple possibilities for the coordination offac-[Re(CO)3(H2O)3]+to a protein have been determined and include binding to Asp, Glu, Arg and His amino-acid residues as well as to the C-terminal carboxylate in the vicinity of Leu and Pro. The large number of rhenium metal complex binding sites that have been identified on specific residues thereby allow increased target identification for the design of future radiopharmaceuticals. The core experimental concept involved the use of state-of-art tuneable synchrotron radiation at the Diamond Light Source to optimize the rhenium anomalous dispersion signal to a large value (f′′ of 12.1 electrons) at itsLIabsorption edge with a selected X-ray wavelength of 0.9763 Å. At the Cu Kα X-ray wavelength (1.5418 Å) thef′′ for rhenium is 5.9 electrons. The expected peak-height increase owing to the optimization of the Ref′′ was therefore 2.1. This X-ray wavelength tuning methodology thereby showed the lower occupancy rhenium binding sites as well as the occupancies of the higher occupancy rhenium binding sites.

Tele-Substitution Reactions in the Synthesis of a Promising Class of Antimalarials

2020 ◽  
Author(s):  
Marat Korsik ◽  
Edwin Tse ◽  
David Smith ◽  
William Lewis ◽  
Peter J. Rutledge ◽  
...  
Keyword(s):  
Heterocyclic Ring ◽  
Ring System ◽  
Substitution Reactions ◽  
Laboratory Notebook ◽  
Polar Solvents ◽  
X Ray ◽  
X Ray Crystallography ◽  
The Core ◽  
Nmr Data

<p></p><p>We have discovered and studied a <i>tele</i>substitution reaction in a biologically important heterocyclic ring system. Conditions that favour the <i>tele</i>-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base, or the use of softer nucleophiles, less polar solvents and larger halogens on the electrophile. Using results from X-ray crystallography and isotope labelling experiments a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the <i>in vivo </i>active anti-plasmodium compounds of Series 4 of the Open Source Malaria consortium.</p> <p> </p> <p>Archive of the electronic laboratory notebook with the description of all conducted experiments and raw NMR data could be accessed via following link <a href="https://ses.library.usyd.edu.au/handle/2123/21890">https://ses.library.usyd.edu.au/handle/2123/21890</a> . For navigation between entries of laboratory notebook please use file "Strings for compounds in the article.pdf" that works as a reference between article codes and notebook codes, also this file contain SMILES for these compounds. </p><br><p></p>

scholarly journals Structures of Rhodopseudomonas palustris RC-LH1 complexes with open or closed quinone channels

2021 ◽  
Vol 7 (3) ◽  
pp. eabe2631
Author(s):  
David J. K. Swainsbury ◽  
Pu Qian ◽  
Philip J. Jackson ◽  
Kaitlyn M. Faries ◽  
Dariusz M. Niedzwiedzki ◽  
...  
Keyword(s):  
Binding Sites ◽  
Rhodopseudomonas Palustris ◽  
Ring Closure ◽  
Light Harvesting Complex ◽  
The Core ◽  
Quinone Binding ◽  
Cryo Electron Microscopy ◽  
Unique Protein ◽  
Center Light ◽  
Resolution Structure

The reaction-center light-harvesting complex 1 (RC-LH1) is the core photosynthetic component in purple phototrophic bacteria. We present two cryo–electron microscopy structures of RC-LH1 complexes from Rhodopseudomonas palustris. A 2.65-Å resolution structure of the RC-LH114-W complex consists of an open 14-subunit LH1 ring surrounding the RC interrupted by protein-W, whereas the complex without protein-W at 2.80-Å resolution comprises an RC completely encircled by a closed, 16-subunit LH1 ring. Comparison of these structures provides insights into quinone dynamics within RC-LH1 complexes, including a previously unidentified conformational change upon quinone binding at the RC QB site, and the locations of accessory quinone binding sites that aid their delivery to the RC. The structurally unique protein-W prevents LH1 ring closure, creating a channel for accelerated quinone/quinol exchange.

scholarly journals The role of AGN activity in the building up of the BCG at z ∼ 1.6

2019 ◽  
Vol 15 (S356) ◽  
pp. 280-284
Author(s):  
Angela Bongiorno ◽  
Andrea Travascio
Keyword(s):  
Galaxy Cluster ◽  
Cluster Galaxy ◽  
X Ray ◽  
Groups Of Galaxies ◽  
Star Forming ◽  
The Core ◽  
The Galaxy ◽  
Multi Wavelength

AbstractXDCPJ0044.0-2033 is one of the most massive galaxy cluster at z ∼1.6, for which a wealth of multi-wavelength photometric and spectroscopic data have been collected during the last years. I have reported on the properties of the galaxy members in the very central region (∼ 70kpc × 70kpc) of the cluster, derived through deep HST photometry, SINFONI and KMOS IFU spectroscopy, together with Chandra X-ray, ALMA and JVLA radio data.In the core of the cluster, we have identified two groups of galaxies (Complex A and Complex B), seven of them confirmed to be cluster members, with signatures of ongoing merging. These galaxies show perturbed morphologies and, three of them show signs of AGN activity. In particular, two of them, located at the center of each complex, have been found to host luminous, obscured and highly accreting AGN (λ = 0.4−0.6) exhibiting broad Hα line. Moreover, a third optically obscured type-2 AGN, has been discovered through BPT diagram in Complex A. The AGN at the center of Complex B is detected in X-ray while the other two, and their companions, are spatially related to radio emission. The three AGN provide one of the closest AGN triple at z > 1 revealed so far with a minimum (maximum) projected distance of 10 kpc (40 kpc). The discovery of multiple AGN activity in a highly star-forming region associated to the crowded core of a galaxy cluster at z ∼ 1.6, suggests that these processes have a key role in shaping the nascent Brightest Cluster Galaxy, observed at the center of local clusters. According to our data, all galaxies in the core of XDCPJ0044.0-2033 could form a BCG of M* ∼ 1012Mȯ hosting a BH of 2 × 108−109Mȯ, in a time scale of the order of 2.5 Gyrs.

scholarly journals A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shin-ichiro Hattori ◽  
Nobuyo Higashi-Kuwata ◽  
Hironori Hayashi ◽  
Srinivasa Rao Allu ◽  
Jakka Raghavaiah ◽  
...  
Keyword(s):  
Small Molecule ◽  
Covalent Bond ◽  
Amino Acid Residues ◽  
X Ray ◽  
Viral Breakthrough ◽  
Main Protease ◽  
Small Molecule Compound ◽  
Polar Interactions ◽  
High Concentrations

AbstractExcept remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (Mpro). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 with EC50 values of 15 ± 4 and 4.2 ± 0.7 μM for GRL-1720 and 5h, respectively. Remdesivir permitted viral breakthrough at high concentrations; however, compound 5h completely blocks SARS-CoV-2 infection in vitro without viral breakthrough or detectable cytotoxicity. Combination of 5h and remdesivir exhibits synergism against SARS-CoV-2. Additional X-ray structural analysis show that 5h forms a covalent bond with Mpro and makes polar interactions with multiple active site amino acid residues. The present data suggest that 5h might serve as a lead Mpro inhibitor for the development of therapeutics for SARS-CoV-2 infection.

Revealing the structural transformation of rutile RuO2via in situ X-ray absorption spectroscopy during the oxygen evolution reaction

2019 ◽  
Vol 48 (21) ◽  
pp. 7122-7129 ◽  
Author(s):  
Chia-Jui Chang ◽  
You-Chiuan Chu ◽  
Hao-Yu Yan ◽  
Yen-Fa Liao ◽  
Hao Ming Chen
Keyword(s):  
Oxygen Evolution ◽  
Structural Transformation ◽  
Absorption Spectroscopy ◽  
Oxygen Evolution Reaction ◽  
The State ◽  
X Ray ◽  
Alkaline Conditions ◽  
X Ray Absorption ◽  
State Of Art

The state-of-art RuO2 catalyst for the oxygen evolution reaction (OER) is measured by using in situ X-ray absorption spectroscopy (XAS) to elucidate the structural transformation during catalyzing the reaction in acidic and alkaline conditions.

scholarly journals Crystallization and Preliminary X-ray Analysis of the Core Particle of Bluetongue Virus

Virology ◽  
1995 ◽  
Vol 210 (1) ◽  
pp. 217-220 ◽  
Author(s):  
J.N. Burroughs ◽  
J.M. Grimes ◽  
P.P.C. Mertens ◽  
D.I. Stuart
Keyword(s):  
Bluetongue Virus ◽  
Core Particle ◽  
X Ray ◽  
The Core

The three-dimensional structure of interleukin-1β

1988 ◽  
Vol 16 (6) ◽  
pp. 949-953 ◽  
Author(s):  
JOHN P. PRIESTLE ◽  
HANS-PETER SCHÄR ◽  
MARKUS G. GRÜTTER
Keyword(s):  
Polypeptide Chain ◽  
Three Dimensional ◽  
Interleukin 1Β ◽  
Dimensional Structure ◽  
X Ray ◽  
Three Dimensional Structure ◽  
R Factor ◽  
The Core ◽  
Internal Sequence ◽  
Network Of Hydrogen Bonds

Summary The three-dimensional structure of human recombinant interleukin-1β has been determined at 0.24 nm resolution by X-ray crystallographic techniques. The partially refined model has a crystallographic R-factor of just under 19%. The structure is composed of 12 β-strands forming a complex network of hydrogen bonds. The core of the structure can best be described as a tetrahedron whose edges are each formed by two antiparallel β-strands. The interior of this structure is filled with hydrophobic side-chains. There is a 3-fold repeat in the folding of the polypeptide chain. Although this folding pattern suggests gene triplication, no significant internal sequence homology between topologically corresponding residues exists. The folding topology of interleukin-1β is very similar to that described by A. D. McLachlan [(1979) J. Mol. Biol. 133, 557–563] for soybean trypsin inhibitor.

Developing structure-based models to predict substrate specificity of D-group (Type II) molybdenum enzymes: application to a molybdo-enzyme of unknown function from Archaeoglobus fulgidus

2006 ◽  
Vol 34 (1) ◽  
pp. 118-121 ◽  
Author(s):  
E.J. Dridge ◽  
D.J. Richardson ◽  
R.J. Lewis ◽  
C.S. Butler
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Sequence Analysis ◽  
Archaeoglobus Fulgidus ◽  
Substrate Selectivity ◽  
Type Ii ◽  
Amino Acid Residues ◽  
Sequence Alignments ◽  
X Ray ◽  
Group Type

The AF0174–AF0176 gene cluster in Archaeoglobus fulgidus encodes a putative oxyanion reductase of the D-type (Type II) family of molybdo-enzymes. Sequence analysis reveals that the catalytic subunit AF0176 shares low identity (31–32%) and similarity (41–42%) to both NarG and SerA, the catalytic components of the respiratory nitrate and selenate reductases respectively. Consequently, predicting the oxyanion substrate selectivity of AF0176 has proved difficult based solely on sequence alignments. In the present study, we have modelled both AF0176 and SerA on the recently determined X-ray structure of the NAR (nitrate reductase) from Escherichia coli and have identified a number of key amino acid residues, conserved in all known NAR sequences, including AF0176, that we speculate may enhance selectivity towards trigonal planar (NO3−) rather than tetrahedral (SeO42− and ClO4−) substrates.

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