Protein-protein interactions play an important role in cell cycle function and homeostasis, but have proven to be challenging targets to address with small molecule inhibitors.
One of the key challenges with PPI systems is the development of robust and relevant assays.
Current methods for measuring small molecule effects on PPI inhibition such as FP, FRET, ELISA, AlphaScreen, NMR, SPR, or ITC require labeling and/or tethering of the target, or are size limited, all of which directly impact the system being monitored.
In contrast, BSI isn’t limited by label, tethering or size restrictions, thereby enabling true binding and inhibition to be directly monitored.
BSI succeeds in determining the effects of small molecule ligands on protein-protein interactions. In the example below, two small molecules were investigated for their direct binding to a protein-protein interaction related to cholesterol metabolism and homeostasis. Compound 2 can be shown to lower the affinity of the interaction 2x below the native state.
Comparison of the effect of two small molecules on protien receptor binding to a protien target.
BSI succeeds in accurately determining the effect of small molecules on protein fibril aggregation. Here, five small molecules were investigated for their effect on fibril formation for a single aggregating protein involved in the progression of Alzheimer’s disease. Compounds can now be ranked on their ability to prevent aggregation in pre-clinical SAR’s.
Small molecule effects on protein fibril aggregation.
BSI succeeds in measuring the effects on endogenous ligands on protein dimerization. Here, a protein involved in nucleotide biosynthesis is demonstrated to dimerize more effectively when both its native substrate and another substrate analog are present.
Effect of native ligands and substrate analogs on protein dimer formation.
TruBind BSI Technology delivers key benefits in the investigation of protein-protein inhibitors, with no tags, no surface attachments for true binding characterization.
