Rational design of thrombin-derived VFR12 analogs with enhanced antimicrobial, antibiofilm, and anti-inflammatory properties.

ABSTRACT: The worsening crisis of antibiotic resistance demands innovative therapies to combat multidrug-resistant pathogens. In this study, we report the rational design and optimization of VFR12 (VFRLKKWIQKVI), a thrombin C-terminus-derived 12-mer peptide, via systematic amino acid substitutions and stereochemical modifications. A series of 12-mer analogs were synthesized and assessed for antimicrobial activity, cell selectivity, biofilm disruption, and immunomodulatory effects. Six lead candidates (VFR12-a7, VFR12-a8, VFR12-a7(L), VFR12-a8(L), VFR12-a7(L)-d, VFR12-a8(L)-d) demonstrated potent broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria, including multidrug-resistant Pseudomonas aeruginosa with minimal hemolytic activity. Notably, D-amino acid varian

SUBMITTER: Jahan I 

PROVIDER: S-EPMC12630807 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature