Secondary structures tend to be recognizable because they have repeating structural motifs, but mimicry of these does not have to follow such well‐defined patterns. Bioinformatics studies to match side‐chain orientations of a novel hydantoin triazole chemotype (1) to protein‐protein interfaces revealed it tends to align well across parallel and antiparallel sheets, like rungs on a ladder. One set of these overlays was observed for the protein‐protein interaction uPA⋅uPAR. Consequently, chemotype 1 was made with appropriate side‐chains to mimic uPA at this interface. Biophysical assays indicate these compounds did in fact bind uPAR, and elicit cellular responses that affected invasion, migration, and wound healing.

Preferred conformations of several peptidomimetics (specifically, minimalist mimics) were elucidated and compared with protein-protein interfaces on a huge scale, leading to a hypothesis regarding how these compounds mimic protein interface segments.