Lydia I Dewis, Rudrakshula Madhavachary, Christopher Williams, Elisabetta Chiarparin, Eddie L Myers, Craig P Butts, Varinder Kumar Aggarwal
With over 60% of protein-protein interfaces featuring an α-helix, α-helix mimetics as inhibitors of these biomolecular interactions is a prevalent therapeutic strategy. However, methods to control the conformation of mimetics, thus enabling maximum efficacy, such as backbone stapling, can be restrictive. Alternatively, conformation can be controlled through the introduction of destabilizing interactions, such as the syn-pentane interaction. This tactic, which is often adopted by Nature, is not a common feature of lead optimization, presumably owing to the significant synthetic effort required...
April 5, 2023: Angewandte Chemie