Development of a Novel Sub Picomolar Method for Microscale Thermophoresis

Tech ID: 23T094

­Advantages:

  • Cost-effective with minimal sample requirements.
  • Label-free detection preserves native molecular states.
  • Real-time analysis for dynamic interactions.

Summary:

Microscale thermophoresis (MST) is a method used to detect and analyze interactions between molecules. Current instrument detection limitations dictate that binding events that occur at concentrations less than one picomolar (< pM) cannot be accurately measured because the ratio between fluorescently dyed molecules and analytes reaches a threshold below detection. This presents a challenge for current measurements of many biological mechanisms in which interactions between proteins and ligands occur at sub picomolar levels.

This technology presents a new method able to detect stimulator of interferon genes (STING) -ligand interactions, which leverages a competition assay between STING along with the signaling ligand 2’,3’-cGAMP. This enables the precise estimation of molecular interactions at exceptionally low analyte concentrations. By utilizing the oligomeric properties of STING, the technique overcomes current limitations in detecting binding events below one picomolar, significantly expanding its applicability in studying various biological mechanisms. Additionally, the method offers valuable analytical data for drug discovery screening, stability assessment, and detection of multiple binding events. The findings represent a significant technological advancement with promising implications for scientific research and medical applications.

Demonstrates significant evidence of three simultaneous interactions with STING recorded using a single compound. These interactions occur within the high affinity area, with concentrations below one picomolar, suggesting that they are likely a result of conformational changes or effects on the STING oligomeric state. The decrease in Fnorm values with increasing concentration indicates progressive breakdown of STING oligomers during thermophoresis.

Desired Partnerships: 

  • License
  • Sponsored Research
  • Co-Development

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