Journal of Peptide Science 2026: WDGL — A Tetrapeptide From Ulva Prolifera Activates Keap1-Nrf2 Antioxidant Pathway in Cellular Stress Models
A Journal of Peptide Science paper reported a novel four-amino-acid peptide WDGL (Trp-Asp-Gly-Leu) derived from Ulva prolifera — the green algae species responsible for major coastal blooms in East Asia. The peptide was identified through virtual screening of marine-derived peptide libraries, binds Keap1 at key residues, and activates the Nrf2 antioxidant pathway in cellular oxidative-stress models. In vitro pharmacokinetic profiling showed favorable properties for further development. The mechanistic rationale: Keap1-Nrf2 activation drives expression of antioxidant response element (ARE)-regulated genes including superoxide dismutase, catalase, and glutathione peroxidase, reducing reactive oxygen species (ROS) and oxidative damage. The WDGL work joins a small but growing literature on tetrapeptides as drug-like scaffolds — Aivocode's CAQK brain-injury tetrapeptide being the other May 2026 example. Marine-derived AMP and bioactive peptide discovery remains an underexplored chemistry frontier.