Designing peptides to meet the challenge of the next generation of druggable targets
Targeting protein–protein interactions (PPIs) is a new challenge in expanding druggable space. Cyclic peptides show promise in targeting PPIs and to better understand their structure–activity relationships a research team at Tufts University, USA, has analyzed a series of designed, well-structured cyclic hexapeptides and use simulations and experimental techniques to understand their global structural ensembles. They discovered a previously unappreciated role for β-branched residues in stabilizing specific conformations of cyclic hexapeptides, and their approach shows promise in the prediction of structure–activity relationships for drug development. Their work was rewarded by being on the front cover of Biophysical Journal, Volume 116, Issue 3.