Optimization of peptide foldamer-based artificial retro-aldolase†

Abstract

Due to their predictable and controllable three-dimensional structure, peptide foldamers constitute a class of compounds beneficial for developing functional molecules. One of the most challenging applications is the construction of enzyme-like catalysts. Here, we describe the optimization of peptide foldamers composed of two 9/12/9/10-helices incorporating cis-2-aminocyclopentanecarboxylic acid residues toward retro-aldol activity. Modifications related to helix handedness, interhelical linker rigidity, and active site construction led to highly active retro-aldolase mimetics. NMR measurements confirmed the assumed arrangement of active site residues.