Figure 1.

General scheme for HyCoSuL design and its use for the discovery of selective and sensitive substrates for caspases. HyCoSuL is composed of three sublibraries containing 129 individual natural and unnatural amino acids. Screening results reveal the identity of residues that contribute to activity at a specific position for each caspase. In the example in the colored bars represent the most selective residue when compared with other caspases (not shown in this illustration). Sometimes, but not always, the most selective residue is also the most active. Thus, HyCoSuL is useful not only for the design and synthesis of sensitive caspase substrates, but also for the discovery of caspase substrates with high selectivity