LL-37 · research summary

A portable N-terminal biphenyl motif in LL-37 enhances the activity of short human cathelicidin derivatives.

bioRxiv : the preprint server for biology · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

In vitro structure-activity and mechanistic study of host defense peptide derivatives
“Informed by our prior structure-activity work, we demonstrate that transposition of an N-terminal biphenyl motif from full-length LL-37 onto the previously-described central activity region (residues 18-29) improves activity against gram-negative bacteria by >16-fold.”

Subjects

Gram-negative bacteria and modified cathelicidin peptide scaffolds
“we demonstrate that transposition of an N-terminal biphenyl motif from full-length LL-37 onto the previously-described central activity region (residues 18-29) improves activity against gram-negative bacteria by >16-fold.”

Reported findings

Transposition of an N-terminal biphenyl motif improves activity against gram-negative bacteria by more than 16-fold
“we demonstrate that transposition of an N-terminal biphenyl motif from full-length LL-37 onto the previously-described central activity region (residues 18-29) improves activity against gram-negative bacteria by >16-fold.”
The biphenyl pharmacophore increases inner and outer membrane permeabilization while promoting helical structure
“Mechanistic interrogation reveals that the biphenyl pharmacophore increases both inner and outer membrane permeabilization while promoting helical structure in the 14-mer without directly impacting peptide stability.”
The biphenyl motif activity is transferable to longer cathelicidin scaffolds
“We further improve upon this lead derivative, termed FF-14, using stabilizing modifications such as D-amino acids and C-terminal amidation as well as selected N-lipidation moieties, and demonstrate the transferability of biphenyl motif activity to longer cathelicidin scaffolds.”

Source: PubMed 42817938 · DOI 10.1101/2025.05.22.655619 · all study summaries

Study type

In vitro structure-activity and mechanistic study of host defense peptide derivatives

“Informed by our prior structure-activity work, we demonstrate that transposition of an N-terminal biphenyl motif from full-length LL-37 onto the previously-described central activity region (residues 18-29) improves activity against gram-negative bacteria by >16-fold.”

Reported findings

Transposition of an N-terminal biphenyl motif improves activity against gram-negative bacteria by more than 16-fold

“we demonstrate that transposition of an N-terminal biphenyl motif from full-length LL-37 onto the previously-described central activity region (residues 18-29) improves activity against gram-negative bacteria by >16-fold.”

The biphenyl pharmacophore increases inner and outer membrane permeabilization while promoting helical structure

“Mechanistic interrogation reveals that the biphenyl pharmacophore increases both inner and outer membrane permeabilization while promoting helical structure in the 14-mer without directly impacting peptide stability.”

The biphenyl motif activity is transferable to longer cathelicidin scaffolds

“We further improve upon this lead derivative, termed FF-14, using stabilizing modifications such as D-amino acids and C-terminal amidation as well as selected N-lipidation moieties, and demonstrate the transferability of biphenyl motif activity to longer cathelicidin scaffolds.”