Related ArticlesRecombinant Kinase Production and Fragment Screening by NMR Spectroscopy.
Methods Mol Biol. 2016;1360:35-46
Authors: Han B, Ahn HC
Abstract
During the past decade fragment-based drug discovery (FBDD) has rapidly evolved and several drugs or drug candidates developed by FBDD approach are clinically in use or in clinical trials. For example, vemurafenib, a V600E mutated BRAF inhibitor, was developed by utilizing FBDD approach and approved by FDA in 2011. In FBDD, screening of fragments is the starting step for identification of hits and lead generation. Fragment screening usually relies on biophysical techniques by which the protein-bound small molecules can be detected. NMR spectroscopy has been extensively used to study the molecular interaction between the protein and the ligand, and has many advantages in fragment screening over other biophysical techniques. This chapter describes the practical aspects of fragment screening by saturation transfer difference NMR.
PMID: 26501900 [PubMed - as supplied by publisher]
[NMR paper] Fragment Screening and Druggability Assessment for the CBP/p300 KIX Domain through Protein-Observed (19) F NMR Spectroscopy.
Fragment Screening and Druggability Assessment for the CBP/p300 KIX Domain through Protein-Observed (19) F NMR Spectroscopy.
Fragment Screening and Druggability Assessment for the CBP/p300 KIX Domain through Protein-Observed (19) F NMR Spectroscopy.
Angew Chem Int Ed Engl. 2015 Feb 4;
Authors: Gee CT, Koleski EJ, Pomerantz WC
Abstract
(19) F NMR spectroscopy of labeled proteins is a sensitive method for characterizing structure, conformational dynamics, higher-order assembly, and ligand binding. Fluorination of aromatic side...
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02-05-2015 12:00 PM
Protocol for aerosol-free recombinant production and NMR analysis of prion proteins
Protocol for aerosol-free recombinant production and NMR analysis of prion proteins
Abstract
The central hallmark of prion diseases is the misfolding of cellular prion protein (PrPC) into a disease-associated aggregated isoform known as scrapie prion protein (PrPSc). NMR spectroscopy has made many essential contributions to the characterization of recombinant PrP in its folded, unfolded and aggregated states. Recent studies reporting on de novo generation of prions from recombinant PrP and infection of animals using prion aerosols suggest that...
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06-19-2014 10:21 PM
[NMR paper] Protocol for aerosol-free recombinant production and NMR analysis of prion proteins.
Protocol for aerosol-free recombinant production and NMR analysis of prion proteins.
Related Articles Protocol for aerosol-free recombinant production and NMR analysis of prion proteins.
J Biomol NMR. 2014 Apr 26;
Authors: Rehbein P, Saxena K, Schlepckow K, Schwalbe H
Abstract
The central hallmark of prion diseases is the misfolding of cellular prion protein (PrP(C)) into a disease-associated aggregated isoform known as scrapie prion protein (PrP(Sc)). NMR spectroscopy has made many essential contributions to the characterization...
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04-29-2014 12:04 PM
[NMR paper] The production of recombinant (15)N, (13)C-labelled somatostatin 14 for NMR spectroscopy.
The production of recombinant (15)N, (13)C-labelled somatostatin 14 for NMR spectroscopy.
The production of recombinant (15)N, (13)C-labelled somatostatin 14 for NMR spectroscopy.
Protein Expr Purif. 2014 Mar 31;
Authors: Nespovitaya N, Barylyuk K, Eichmann C, Zenobi R, Riek R
Abstract
Structural studies of human peptide hormone somatostatin 14 (SS14) require high amounts of isotopically labelled SS14 to be produced. Here we report a method for effective production of isotopically labelled SS14. SS14 was expressed as a fusion...
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04-06-2014 02:01 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
Production of recombinant isotopically labelled peptide by fusion to an insoluble par
Production of recombinant isotopically labelled peptide by fusion to an insoluble partner protein: generation of integrin ?v?6 binding peptides for NMR.
Related Articles Production of recombinant isotopically labelled peptide by fusion to an insoluble partner protein: generation of integrin ?v?6 binding peptides for NMR.
Mol Biosyst. 2010 Oct 18;
Authors: Wagstaff JL, Howard MJ, Williamson RA
The integrin ?v?6 is up-regulated in several cancers and has clinical potential for both tumour imaging and therapy. Peptide ligands have been developed...
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10-19-2010 04:51 PM
[NMR paper] Recombinant production of the p10CKS1At protein from Arabidopsis thaliana and 13C and
Recombinant production of the p10CKS1At protein from Arabidopsis thaliana and 13C and 15N double-isotopic enrichment for NMR studies.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles Recombinant production of the p10CKS1At protein from Arabidopsis thaliana and 13C and 15N double-isotopic enrichment for NMR studies.
Protein Expr Purif. 1999 Jun;16(1):144-51
Authors: Landrieu I, Casteels P, Odaert B, De Veylder L, Portetelle D, Lippens G, Van Montagu M, Inzé D
The CKS1At...
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08-21-2010 04:03 PM
Enhanced production and isotope enrichment of recombinant glycoproteins produced in c
Abstract NMR studies of post-translationally modified proteins are complicated by the lack of an efficient method to produce isotope enriched recombinant proteins in cultured mammalian cells. We show that reducing the glucose concentration and substituting glutamate for glutamine in serum-free medium increased cell viability while simultaneously increasing recombinant protein yield and the enrichment of non-essential amino acids compared to culture in unmodified, serum-free medium. Adding dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, further improves cell viability, recombinant...
Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.
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