TARGET IMMOBILIZED NMR SCREENING
TINS has been validated on a wide range of targets including viral proteins, proteases, kinases, Protein-Protein Interaction targets, molecular chaperones and membrane proteins such as GPCRs.
TINS uses a single sample of the target and a reference protein that have been immobilized on sepharose based resin. Screens are carried out by repeated cycles of i) fragment application, ii) assaying for binding and iii) fragment removal.
- Applicable to a broad range of targets, including unstable proteins and membrane proteins.
- Requires only a single sample of the target, between 10-20 nmol.
- Targets are functionally immobilized using various conjugation techniques.
- Comparative technique, i.e. use of a reference protein: high level of ligand specificity.
- Direct detection of binding, no deconvolution required.
- Fast: 1,500 compounds screened in 3-4 days, complete hit discovery project finished within 1-2 months.
- Possibility to screen a customers library.
- Fragment Screening of GPCRs Using Biophysical Methods: Identification of Ligands of the Adenosine A2A Receptor with Novel Biological Activity. Chen, ACS Chem. Biol., 2012
- Fragment Screening of Stabilized G-Protein Coupled Receptors using Biophysical Methods. Congreve, Method. Enzymol., 2011
- Application of Fragment-Based Drug Discovery to Membrane Proteins: Identification of Ligands of the Integral Membrane Enzyme DsbB. Früh, Chem. Biol., 2010
- Target Immobilization as a Strategy for NMR-Based Fragment Screening: Comparison of TINS, STD, and SPR for Fragment Hit Identification. Kobayashi, J. Biomol. Screen., 2010
- Target Immobilization and NMR Screening of Fragments in Early Drug Discovery. Siegal, Curr. Top. Med. Chem., 2009
- Integration of Fragment Screening and Library Design. Siegal, Drug Disc. Today, 2007
- Development of a Dual Cell, Flow-Injection Sample Holder, and NMR Probe for Comparative Ligand-Binding Studies. Marquardsen, J. Mag. Reson., 2006
- TINS, Target Immobilized NMR Screening: An Efficient and Sensitive New Method for Ligand Discovery. Vanwetswinkel, Chem. Biol., 2005