Synthetic Diversity and Catalytic Mechanism of Peptide Dendrimers

Abstract

Peptide dendrimers composed of alternating sequences of natural amino acids and branching diamino acids are investigated as synthetic enzyme models. The dendrimers can be prepared by solid-phase peptide synthesis and are obtained pure in yields of 5–35%. Peptide dendrimers with surface histidine residues catalyze ester hydrolysis reaction with enzyme-like kinetics, including substrate binding (KM), catalytic turnover (kcat), and rate acceleration kcat/kuncat = 1000–20'000. Mechanistic investigation by substrate variation, pH-profile, and isothermaltitration calorimetry show that the catalytic effect is caused by positive interaction between the histidine side-chains and creation of a hydrophobic microenvironment for substrate binding.