Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of â??poised fragmentsâ?? with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process.
Structural investigation of glycan recognition by the ERAD quality control lectin Yos9
Structural investigation of glycan recognition by the ERAD quality control lectin Yos9
Abstract
Yos9 is an essential component of the endoplasmic reticulum associated protein degradation (ERAD) system that is responsible for removing terminally misfolded proteins from the ER lumen and mediating proteasomal degradation in the cytosol. Glycoproteins that fail to attain their native conformation in the ER expose a distinct oligosaccharide structure, a terminal α1,6-linked mannose residue, that is specifically recognized by the mannose 6-phoshate...
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11-25-2018 06:02 AM
Fluorine pharma: Quality control by NMR
Fluorine pharma: Quality control by NMR
http://www.spectroscopynow.com/common/images/thumbnails/1600c98c38f.jpgRoutine analysis and quality control of fluorine-containing pharmaceuticals could now be possible with the application of the relatively simple and straightforward technique of fluorine-19 nuclear magnetic resonance (NMR) spectroscopy, according to researchers in Kenya and Germany.
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12-01-2017 08:23 AM
Low-Field Permanent Magnets for Industrial Process and Quality Control
Low-Field Permanent Magnets for Industrial Process and Quality Control
Publication date: Available online 30 September 2013
Source:Progress in Nuclear Magnetic Resonance Spectroscopy</br>
Author(s): J. Mitchell , L.F. Gladden , T.C. Chandrasekera , E.J. Fordham</br>
In this review we focus on the technology associated with lowfield NMR. We present the current state-of-the-art in low-field NMR hardware and experiments, considering general magnet designs, rf performance, data processing and interpretation. We provide guidance on obtaining the optimum results from...
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09-30-2013 03:48 PM
[NMR paper] HTS by NMR of Combinatorial Libraries: A Fragment-Based Approach to Ligand Discovery.
HTS by NMR of Combinatorial Libraries: A Fragment-Based Approach to Ligand Discovery.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-cellhub.gif Related Articles HTS by NMR of Combinatorial Libraries: A Fragment-Based Approach to Ligand Discovery.
Chem Biol. 2013 Jan 24;20(1):19-33
Authors: Wu B, Zhang Z, Noberini R, Barile E, Giulianotti M, Pinilla C, Houghten RA, Pasquale EB, Pellecchia M
Abstract
Fragment-based ligand design (FBLD) approaches have become more widely used in drug discovery...
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02-03-2013 10:19 AM
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
Target immobilization as a strategy for NMR-based fragment screening: comparison of TINS, STD, and SPR for fragment hit identification.
J Biomol Screen. 2010 Sep;15(8):978-89
Authors: Kobayashi M, Retra K, Figaroa F, Hollander JG, Ab E, Heetebrij RJ, Irth H, Siegal G
Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing...
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01-13-2011 12:00 PM
Real-time NMR Studies of the Folding & Mechanisms of Protein Quality Control Machiner
Real-time NMR Studies of the Folding & Mechanisms of Protein Quality Control Machineries
* In the context of a project funded by European Research Council, two postdoctoral positions are available at the Structural Biology Institute in Grenoble (France) to study by real-time NMR the Folding & Mechanisms of Protein Quality Control (PQC) Machineries. Selected candidates will use latest NMR technologies developed at IBS to characterize self-assembly and functionally important structural rearrangements of large PQC machineries isolated at IBS.
* The laboratory host…
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NMR quality control of fragment libraries for screening
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