Chemical probes that mimic a pharmacophore, ligand, or lead compound are of increasing interest for target identification and validation, protein profiling, imaging, or other applications in chemical biology. However, synthesis of the ideal probe is not trivial as even slight structural alterations may have unpredictable effects on target binding and selectivity.1 The synthesis and screening of several analogs is thus often necessary to optimize the outcome of an assay.
In partnership with Pfizer chemists, we have compiled a collection of trifunctional building blocks to enable development of probes. Each possesses three components:
Figure 1.Trifunctional Building Blocks
Trifunctional probe building blocks service synthetic chemical biologists in two key ways.
These trifunctional scaffolds have been valuable in several applications requiring probe development, such as the examples below.1-3, 6-12 To access these probes, a suggested building block is listed next to each structure.
Figure 2.Trifunctional Scaffolds
Similar connectivity groups streamline the functionalization of one bioactive small molecule into a library of potential probes.1 For instance, by using the CO2H-containing building blocks with a ligand’s NH2, a panel of seven probe analogs can be accessed.
Figure 3.Target-specific Probe Library
Figure 4.Benzophenones, Diazirines, and Sulfonyl Fluorides