LL-37

LL-37 is the 37-residue C-terminal fragment released from the cathelicidin precursor protein hCAP18, named for its two leading leucines and its length. It is strongly cationic, carrying a net positive charge at physiological pH, and folds into an amphipathic alpha-helix in which hydrophobic and charged residues segregate onto opposite faces.

That amphipathicity is the mechanism. Rather than binding a defined receptor pocket, the peptide associates electrostatically with negatively charged membrane surfaces and inserts its hydrophobic face into the lipid bilayer, permeabilising it. Selectivity for bacterial over mammalian membranes derives from the greater density of anionic lipids in bacterial envelopes, which makes membrane composition rather than receptor expression the determinant of activity.

The in-vitro literature is unusually diverse in method because a membrane-active peptide is characterised by biophysics as much as by biology. Liposome leakage assays using dye-loaded vesicles measure permeabilisation directly, and circular dichroism is used to confirm that the peptide adopts helical structure on membrane binding, since it is largely disordered in aqueous solution.

Alongside antimicrobial work, reported investigation covers immune signalling roles: chemotactic activity toward immune cell populations, and modulation of responses to bacterial products in cultured cells. Biofilm-related work is a further strand, examining activity against organised bacterial communities rather than free-swimming cells.

Reversed-phase HPLC purity and mass spectrometry identity are reported per lot on the Certificate of Analysis, with deletion sequences the dominant impurity class at this length. There is no cysteine and no terminal modification.

The attribute that matters most for this particular peptide is residual trifluoroacetate. Purification leaves TFA as the counter-ion for a strongly cationic sequence, and TFA is biologically active in culture at concentrations well below those that register on a peptide purity assay. For a peptide whose reported activity is antimicrobial and cytotoxic in nature, residual TFA is a direct confounder rather than an incidental impurity, and a lot intended for cell-based work is worth checking on that basis.