Related ArticlesTINS, target immobilized NMR screening: an efficient and sensitive method for ligand discovery.
Chem Biol. 2005 Feb;12(2):207-16
Authors: Vanwetswinkel S, Heetebrij RJ, van Duynhoven J, Hollander JG, Filippov DV, Hajduk PJ, Siegal G
We propose a ligand screening method, called TINS (target immobilized NMR screening), which reduces the amount of target required for the fragment-based approach to drug discovery. Binding is detected by comparing 1D NMR spectra of compound mixtures in the presence of a target immobilized on a solid support to a control sample. The method has been validated by the detection of a variety of ligands for protein and nucleic acid targets (K(D) from 60 to 5000 muM). The ligand binding capacity of a protein was undiminished after 2000 different compounds had been applied, indicating the potential to apply the assay for screening typical fragment libraries. TINS can be used in competition mode, allowing rapid characterization of the ligand binding site. TINS may allow screening of targets that are difficult to produce or that are insoluble, such as membrane proteins.
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...
nmrlearner
Journal club
0
01-13-2011 12:00 PM
[NMR paper] Application of NMR SHAPES screening to an RNA target.
Application of NMR SHAPES screening to an RNA target.
Related Articles Application of NMR SHAPES screening to an RNA target.
J Am Chem Soc. 2003 Dec 24;125(51):15724-5
Authors: Johnson EC, Feher VA, Peng JW, Moore JM, Williamson JR
Several NMR screening techniques have been developed in recent years to aid in the identification of lead drug compounds. These NMR methods have traditionally been used for protein targets, and here we examine their applicability for an RNA target. We used the SHAPES compound library to test three different NMR...
nmrlearner
Journal club
0
11-24-2010 09:16 PM
[NMR paper] A general NMR method for rapid, efficient, and reliable biochemical screening.
A general NMR method for rapid, efficient, and reliable biochemical screening.
Related Articles A general NMR method for rapid, efficient, and reliable biochemical screening.
J Am Chem Soc. 2003 Nov 26;125(47):14620-5
Authors: Dalvit C, Ardini E, Flocco M, Fogliatto GP, Mongelli N, Veronesi M
High-throughput screening is usually the method of drug-lead discovery. It is now well accepted that, for a functional assay, quality is more important than quantity. The ligand-based or protein-based NMR screening methodologies for detecting compounds...
nmrlearner
Journal club
0
11-24-2010 09:16 PM
[NMR paper] NMR spectroscopy techniques for screening and identifying ligand binding to protein r
NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors.
Related Articles NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors.
Angew Chem Int Ed Engl. 2003 Feb 24;42(8):864-90
Authors: Meyer B, Peters T
Binding events of ligands to receptors are the key for an understanding of biological processes. Gaining insight into protein-protein and protein-ligand interactions in solution has recently become possible on an atomic level by new NMR spectroscopic techniques....
nmrlearner
Journal club
0
11-24-2010 09:01 PM
[NMR paper] Microdrop screening: a rapid method to optimize solvent conditions for NMR spectrosco
Microdrop screening: a rapid method to optimize solvent conditions for NMR spectroscopy of proteins.
Related Articles Microdrop screening: a rapid method to optimize solvent conditions for NMR spectroscopy of proteins.
J Biomol NMR. 1998 Nov;12(4):493-9
Authors: Lepre CA, Moore JM
Determining appropriate solvent conditions is a crucial first step for carrying out NMR spectroscopy of proteins, but rapid and efficient methods for doing so are currently lacking. Microdrop screening examines a large number of different solvent conditions using...
nmrlearner
Journal club
0
11-17-2010 11:15 PM
Efficient protein production method for NMR using soluble protein tags with cold shoc
Efficient protein production method for NMR using soluble protein tags with cold shock expression vector
Abstract The E. coli protein expression system is one of the most useful methods employed for NMR sample preparation. However, the production of some recombinant proteins in E. coli is often hampered by difficulties such as low expression level and low solubility. To address these problems, a modified cold-shock expression system containing a glutathione S-transferase (GST) tag, the pCold-GST system, was investigated. The pCold-GST system successfully expressed 9 out of 10 proteins...
nmrlearner
Journal club
0
09-18-2010 04:53 AM
Efficient protein production method for NMR using soluble protein tags with cold shoc
Efficient protein production method for NMR using soluble protein tags with cold shock expression vector.
Related Articles Efficient protein production method for NMR using soluble protein tags with cold shock expression vector.
J Biomol NMR. 2010 Sep 16;
Authors: Hayashi K, Kojima C
The E. coli protein expression system is one of the most useful methods employed for NMR sample preparation. However, the production of some recombinant proteins in E. coli is often hampered by difficulties such as low expression level and low solubility. To...
nmrlearner
Journal club
0
09-17-2010 04:14 PM
[NMR paper] High resolution NMR for screening ligand/protein binding.
High resolution NMR for screening ligand/protein binding.
Related Articles High resolution NMR for screening ligand/protein binding.
Curr Opin Drug Discov Devel. 1999 Jul;2(4):396-400
Authors: Shapiro MJ, Wareing JR
High resolution NMR spectroscopy has provided a versatile tool for assessing ligand/receptor interactions. NMR-based methods are currently being investigated which may prove valuable for compound screening. These techniques include the use of chemical shift perturbations, the monitoring of translational diffusion and the...
TINS, target immobilized NMR screening: an efficient and sensitive method for ligand
Linear Mode
