Inhibition of chymotrypsin by a self-assembled DNA quadruplex functionalized with cyclic peptide binding fragments

The efficient binding and inhibition of α-chymotrypsin (ChT) by a self-assembled DNA quadruplex with protein recognition fragments appended on the 5'-ends of the assembled G-quartet was reported. The peptide loops were constructed such that they are broadly complementary to the cationic and hydrophobic active site region of ChT. The single-strand peptide loop adduct presents only a single monomeric peptide loop to the protein and displays the weakest inhibition. The factorial velocities for the hydrolysis of N-benzoyl tyrosine p-nitroanilide by ChT as a function of preincubation time for different concentrations show a two-step mechanism of inhibition. The protein fragment is also found to display the highest inhibition potency for ChT and also found to be a good inhibitor.