Investigation of the Effect of Turn Residues on Tetrapeptide Aldol Catalysts with β-Turn Propensity.

Abstract

Peptide catalysts for a wide diversity of reaction types contain a common motif-residues that bias the sequence toward β-turn secondary structure. In this work, we explore what role that secondary structure plays in the catalysis of aldol reactions for primary amine tetrapeptide aldol catalysts. Using a lead tetrapeptide β-turn catalytic sequence, we varied the i + 1 and i + 2 residues to amino acids that would affect the β-turn propensity. We then studied the correlation between secondary structure, aldol rate enhancement, and stereoselectivity of the reaction between hydroxyacetone and 4-nitrobenzaldehyde. Using the i + 3 amide chemical shift as a measure of β-turn character, we found a rough correlation between the peptide structure and reaction kinetics but minimal effect on stereoselectivity. These trends may help aid the design of future catalytic sequences.