Solution- and Solid-Phase Synthesis of Bis-Benzamide Libraries as α-Helix Mimetics and Their Evaluation on Inhibitory Activity to Prostate Cancer

摘要

Mimicking α-helices is a promising approach for the treatment of human diseases since they are often involved in protein-protein interactions and modulate various disease pathways. Toward this goal, non-peptidic frameworks that have pre-organized conformations have been developed for reproducing side chain functional groups in an α-helix. They have served as an effective tool to target α-helical structures offering advantages, such as proteolytic stability and cell permeability [1]. While α-helix mimetics are typically designed based on the structure of an ideal α-helix, helical segments in many proteins frequently differ from the flawless one because the locations of side chains subtly deviate from the perfect helical geometry. Thus, fine-tuning of substituents' structures and positions and constructing libraries of α-helix mimetics would facilitate rapid achievement of optimal interactions with target proteins [2].