Figure 9.

Focused chemical evolution. A “pool of genotypes” is synthesized starting from a set of NP fragments using synthetic strategies that allow for the formation of specific connectivities and thus, the expression of “phenotypes” which may be further derivatized. Due to structural properties such as the number of sp³-hybridized atoms, stereogenic atoms, heteroatoms, and aromaticity, the phenotypes exhibit varying potentials to recognize and interact with proteins, e.g. enzymes. This will become evident upon application to cellular screening platforms which can be monitored for structural changes, e.g. by fluorescence imaging. A variety of data can be observed, combined, and sorted according to desired criteria. Small molecules, which cause a relevant change, are isolated, characterized, and submitted to studies of structure–activity relationships, thereby revealing new chemical information. The outcome is a starting point for successive rounds of mutagenizing synthesis, selection, and identification. For definitions of genotype, phenotype, evolution, and information in different contexts, please see the Supporting Information.