Natural anionic polymer acts as highly efficient trypsin inhibitor based on an electrostatic interaction mechanism

Area of Science:

• Biochemistry
• Polymer Science

Background:

• Trypsin is a key protease in various biological processes.
• Developing effective and safe trypsin inhibitors is crucial for pharmaceutical applications.
• Commercial inhibitors like soybean trypsin inhibitor (STI) have limitations.

Purpose of the Study:

• To investigate the inhibitory potential of sodium alginate (SA) against trypsin.
• To elucidate the mechanism of trypsin inhibition by SA.
• To assess SA as a potential excipient in peptide and protein formulations.

Main Methods:

• Studied the electrostatic interaction between sodium alginate and trypsin.
• Determined the half-maximal inhibitory concentration (IC50) of SA.
• Compared the inhibitory efficacy of SA with commercial soybean trypsin inhibitor (STI).
• Investigated the mechanism of inhibition, differentiating from Ca(2+)-deprivation methods.

Main Results:

• Sodium alginate demonstrated potent trypsin inhibition with an IC50 of 0.05 μg mL(-1).
• SA's inhibitory concentration was approximately 400 times lower than STI.
• The inhibition mechanism involves preventing trypsin active site access to substrates, not denaturation.
• SA functions via electrostatic interactions.

Conclusions:

• Sodium alginate is a highly efficient and cost-effective trypsin inhibitor.
• SA is a safe and innocuous excipient for peptide and protein formulations.
• Its unique inhibition mechanism offers advantages over existing methods.