C3-Symmetric Ligands in Drug Design: When the Target Controls the Aesthetics of the Drug

A number of proteins are able to adopt a homotrimeric spatial conformation. Among these structures, this feature appears as crucial for biologic targets, since it facilitates the design of C3-symmetric ligands that are especially suitable for displaying optimized ligand-target interactions and therapeutic benefits. Additionally, DNA as a therapeutic target, even if its conformation into a superhelix does not correspond to a C3-symmetry, can also take advantage of these C3-symmetric ligands for better interactions and therapeutic effects. For the moment, this opportunity appears to be under-exploited, but should become more frequent with the discovery of new homotrimeric targets such as the SARS-CoV2 spike protein. Besides their potential therapeutic interest, the synthetic access to these C3-symmetric ligands often leads to chemical challenges, although drug candidates with an aesthetic structure are generally obtained.

Automated summary

A number of proteins can adopt a homotrimeric spatial conformation, which is crucial for biologic targets in designing C3-symmetric ligands for optimized ligand-target interactions and therapeutic benefits. Both proteins and DNA can benefit from these ligands, even if their conformation does not correspond to a C3-symmetry. The discovery of new homotrimeric targets, such as the SARS-CoV2 spike protein, is expected to increase the use of these ligands in the future. The synthesis of C3-symmetric ligands presents chemical challenges but can result in aesthetically appealing drug candidates.