Moving LL-37's biphenyl motif onto a short peptide boosts Gram-negative killing
- Transplanting the N-terminal biphenyl motif of full-length LL-37 onto a central 12-residue activity region gave a much more active derivative, FF-14, against Gram-negative bacteria.
- Further tuning used D-amino acids, C-terminal amidation and selected N-lipid groups, and the motif also worked on longer cathelicidin scaffolds.
- Mechanistically, the biphenyl increases inner and outer membrane permeabilization and promotes helicity in the short peptide, without directly changing stability.
- It is presented as a portable way to make short sequences behave more like LL-37.
💡 Points Based on the abstract
A biphenyl as a portable hydrophobic anchor is a neat lipidation-like trick, but membrane-active peptides often trade potency for hemolysis and cytotoxicity, so the window against mammalian cells is the data I'd chase next. Benchmarking against plain N-terminal fatty acids would show whether the biphenyl's helicity effect is truly special.
📄 Paper · Journal of Medicinal Chemistry ↗ A Portable N-Terminal Biphenyl Motif in LL-37 Enhances the Activity of Short Human Cathelicidin Derivatives