Constrained TACC3 peptidomimetics for a non-canonical protein-protein interface elucidate allosteric communication in Aurora-A kinase.

Peptidomimetic design for non-canonical interfaces is less well established than for α-helix and β-strand mediated protein-protein interactions. Using the TACC3/Aurora-A kinase interaction as a model, we developed a series of constrained TACC3 peptide variants with 10-fold increased binding potencies ( ) towards Aurora-A in comparison to the parent peptide. High-affinity is achieved in part by restricting the accessible conformational ensemble of the peptide leading to a more favourable entropy of binding.