Natural Anionic Polymer Acts as Highly Efficient Trypsin Inhibitor Based on an Electrostatic Interaction Mechanism

Sodium alginate (SA), acting as a trypsin inhibitor by means of electrostatic interaction, is studied. The half-maximal inhibitory concentration (IC 50 = 0.05 μg mL −1 ) of this natural anionic polymer is about 400 times lower than that of commercial soybean trypsin inhibitor (STI). Unlike the Ca 2+ -deprivation mechanisms, its inhibition may be attributed to preventing the trypsin active site (TAS) from accessing the macromolecular substrates instead of denaturing it. SA is an efficient, innocuous, and cost-effective inhibitory excipient that can be conveniently used in many peptide and protein dosage formulations.