Lactam bridge replaces oxidation-prone thioether in an IL-11 antagonist peptide
- The oxidation-sensitive thioether in an IL-11-binding peptide was replaced with a lactam bridge, with linker length screened systematically.
- The optimized analog 4L6–16 bound IL-11 with good affinity and antagonized it more strongly than the starting peptide.
- It showed renoprotective effects in both cell and animal models of renal fibrosis.
💡 Points
Swapping a thioether for a lactam is a textbook peptide-stability fix, and it's encouraging that it also improved antagonism rather than just shelf life. Binding in the mid-nanomolar range leaves room to tighten, and proteolytic stability in plasma is the next number I'd ask for.
Development of a Lactam-Bridged Peptide as Interleukin-11 Antagonist for Renal Fibrosis Treatment ↗