LAUSR

Protein−protein interactions (PPIs) are key biological targets for next-generation drug discovery. Peptide-derived molecules are ideal for targeting PPIs because they can closely mimic the binding surfaces presented by the proteins in the PPI. Conformational control represents a major challenge in advancing peptides as PPI modulators for pharmaceutical development. In this issue of ACS Central Science, Philip Dawson and co-workers report an efficient approach to access “stretched” peptides, namely, those with an enforced geometry resembling that of a β-sheet. They accomplish this by installing a strained diyne-containing macrocycle and establishing the role of various modifications to the macrocycle’s structure in altering both the conformation of the peptide backbone and the antibiotic activity.