Fragment screening by SPR and advanced application to GPCRs

Area of Science:

• Biophysics
• Biochemistry
• Pharmacology

Background:

• Surface plasmon resonance (SPR) is a key biophysical technique for screening fragment libraries.
• Its label-free nature and low protein consumption make it suitable for identifying low molecular weight binders.
• SPR biosensor analysis provides crucial affinity and kinetic data for molecular interactions.

Purpose of the Study:

• To discuss the application of SPR in fragment screening, particularly for G-protein coupled receptors (GPCRs).
• To highlight SPR's capability in assessing weak affinities characteristic of fragment compounds.
• To review the state-of-the-art and technical considerations for SPR-based GPCR fragment screening.

Main Methods:

• Utilizing SPR biosensor technology for fragment screening.
• Analyzing binding affinity and kinetics of compound-target interactions.
• Employing SPR for both thermostabilised and solubilised GPCRs.

Main Results:

• SPR enables accurate screening and confirmation of fragment binding to GPCRs.
• Biophysical GPCR assays using SPR are validated against cell-based methods.
• SPR can measure weak affinities of low molecular weight fragments against GPCRs.

Conclusions:

• SPR is a versatile and powerful tool for fragment screening against GPCRs.
• The technique offers advantages in terms of protein consumption and data accuracy.
• SPR fragment screening is advancing drug discovery for membrane protein targets.