Regenerable Surface Plasmon Resonance (SPR) Surfaces for Reliable, Cost-Effective, and Wide-Ranging Applications

Traditional SPR-based drug discovery efforts in the small-molecule space have revolved around single-use chips for screening and hit-to-lead efforts. Inspired by recent technological advances, we have established simple regenerable protocols that can (1) accommodate target-proteins with common tags such as His- and Avi-, (2) reach sufficient surface density for small-molecule testing, and (3) maintain a stable-baseline for accurate kinetic measurements.

These protocols provide effective use of a chip surface reproducibly, saving time and reducing waste.  Additionally, the simple replenishment process allows for special applications such as testing challenging targets with poor longevity on the surface, or quasi-stable multi-component complexes. The process can efficiently monitor covalent ligand reactivity, a process that was previously considered low-throughput and expensive.  These regeneration strategies are readily applicable for late-stage characterizations by measuring affinities of candidates with long residence times, leveraging residual occupancy (a/k/a chaser) methodologies.

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