Fragment Library Screening

ZoBio offers its proprietary TINS technology for ligand screening studies on our own, highly validated fragment library or the customer’s.  TINS is a powerful approach to hit discovery that has been validated on a wide range of targets including viral proteins, proteases, kinases, Protein-Protein Interaction targets, molecular chaperones and membrane proteins including GPCRs.

TINS screen on a protein-protein interaction target

In TINS, binding is best represented by the ratio of the heights of each peak of a compound in the presence of the reference and the target (the T/R ratio). The graph below presents the number of compounds with a T/R in each of the bins presented on the x-axis. This gives a profile of the screen that is unique for each target.

The blue dots are the T/R of the peptide native ligand demonstrating the functionality of the immobilized target. The assay has been repeated throughout the screen to insure the integrity of the target. The red and green dots represent the T/R of 2 known, non-binders. The maximum of the profile is centered at a T/R of 1, indicating that the majority of fragments do not bind or bind equally and therefore, non-specifically, to the target and reference proteins. Few fragments bind the reference (the PH domain of human Akt1) as expected, whereas many bind the target. A cutoff for hit selection has been chosen at the sudden increase in the histogram at T/R ~0.4. Of the approximately 1,400 fragments screened, 90 hits were identified and subsequently validated using protein observered NMR.

Properties of the ZoBio Fragment library

Approximately 1,500 compounds evenly distributed in 4 themes. Siegal et al. DDT 2007

It is also possible to format the customer’s library for TINS screening.

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