Synthesis and evaluation of amino acid derivatives as protease inhibitors on cathepsin G trypsin and chymotrypsin

Abstract

In the course of this research work, a series of peptides or amino acid derivatives were synthesized by mixed anhydride method. All of these synthetic peptides are novel. These synthetic compounds were purified by fractional recrystallisation. The purity of the end products was confirmed by thin-layer chromatography and elemental analysis. All the structures were thoroughly elucidated by infrared, proton and carbon-13 nuclear magnetic resonance spectroscopies. The effectiveness of the synthetic compounds as inhibitors was determined against three serine proteases namely trypsin, chymotrypsin and cathepsin G at the physiological conditions. The results showed that all the synthetic compounds gave a poor inhibitory activity against trypsin, but they are quite good inhibitors against chymotrypsin. However, at the testing conditions, cathepsin G gave such a low activity that it was impossible to test with the synthetic compounds. All the synthetic inhibitors were also tested to determine the type of inhibition against chymotrypsin by the interpretation of Lineweaver-Burk plots. The results showed that all of them are competitive inhibitors.