Key Highlights
• Carterra Ultra® offers the enhanced speed and sensitivity necessary to support Fragment-Based Lead Discovery (FBLD).
• Ultra’s large ligand array allows for many targets, off targets, mutants, and multiple species to be measured in parallel; a 100-fold enhancement over other SPR systems.
• Utilise ready-made panels of biotinylated-proteins to standardise the assay parameters so you can move directly to finding hits and drive your medicinal chemistry programmes.

Fragment-Based Lead Discovery (FBLD) has emerged as a core approach to early-stage hit finding in drug discovery programmes.¹ This form of drug discovery is distinguished by the screening of libraries of very small chemical compounds (heavy atom count < 17), that bind with low affinity (double digit micromolar to millimolar KD) to therapeutic targets. Screening small compounds allows for an efficient sampling of the chemical space relevant to medicinal chemistry. The identified binders, in concert with X-ray co-crystal or cryo-electron microscopy structures, serve to provide a map of how chemical matter can interact efficiently with the targets.

The first step in FBLD is the screening of a fragment library using one or more hit-finding technologies capable of detecting the low-affinity transient interactions of very small compounds with drug targets. Surface Plasmon Resonance (SPR) has found widespread use in industry and academia for initiating and supporting FBLD programmes from hit finding through lead optimisation. SPR offers a broad dynamic range (mM to pM), sensitivity (100 kDa proteins), applicability to a wide range of target classes including membrane proteins, cost effectiveness, flexibility (direct binding and competition formats), and throughput.²^,³ The throughput of various commercial SPR platforms has improved with successive generations of instruments through a combination of reduced sample injection cycle times and increased ligand capacity allowing the testing of a single compound against multiple proteins simultaneously. This capability is frequently used to increase the target throughput of an SPR lab in supporting screening and hit-to-lead campaigns, provide information about mutants and off targets, and compile data on target ligandability.