An Effective Modification Strategy to Build Multifunctional Peptides Based on a Trypsin Inhibitory Peptide of the...

Area of Science:

• Biochemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Peptides with antimicrobial or protease inhibitory activity are potential therapeutic agents.
• Challenges include peptide cytotoxicity and susceptibility to hydrolysis, limiting clinical applications.
• Structural modification offers a strategy to enhance peptide efficacy and safety.

Purpose of the Study:

• To synthesize and evaluate analogues of the Kunitz-type peptide OSTI-1949 from *Odorrana schmackeri*.
• To investigate the antimicrobial, anticancer, and trypsin inhibitory activities of designed analogues.
• To assess the safety profile, particularly cytotoxicity, of the modified peptides.

Main Methods:

• Chemical synthesis of the parent peptide OSTI-1949 and four designed analogues.
• Evaluation of antimicrobial and anticancer activities using cell-based assays.
• Assessment of trypsin inhibitory activity.
• Determination of hemolytic activity and cytotoxicity against normal cells (HaCaT).

Main Results:

• Synthesized analogues exhibited multi-functional activities, including antimicrobial, anticancer, and trypsin inhibition.
• Analogue OSTI-2461 demonstrated enhanced anticancer activity against cancer cell lines without significant cytotoxicity to normal HaCaT cells.
• No significant changes in hemolytic activity were observed at the highest tested concentration.

Conclusions:

• Structural modification of the natural Kunitz-type peptide OSTI-1949 successfully improved biological activity.
• The developed analogues show promise as therapeutic candidates with retained low cytotoxicity.
• Helicity enhancement through artificial α-helix and ß-sheet structures is a viable strategy for developing novel bioactive peptides.