LL37

LL-37 is the mature antimicrobial peptide cleaved from hCAP18, the single cathelicidin precursor in humans. The name is literal — thirty-seven residues, the first two of which are leucine. It is expressed by neutrophils, macrophages and epithelial surfaces, and its expression rises at sites of infection or injury.

In solution it folds into an amphipathic alpha helix: hydrophobic residues on one face, cationic on the other. That geometry is the mechanism.

The cationic face is attracted to the negatively charged surface of bacterial membranes; the hydrophobic face inserts into the lipid bilayer. The result is loss of membrane integrity. Mammalian membranes, which carry less negative surface charge and contain cholesterol, are affected far less — that differential is what makes it selective.

Beyond direct antimicrobial action, LL-37 is studied as a signalling molecule in its own right:

• Chemotaxis — recruitment of neutrophils, monocytes and T cells

• Neutralisation of bacterial lipopolysaccharide, damping the endotoxin response

• Wound closure models, where it is examined for effects on epithelial migration

• Biofilm research, an area where membrane-acting agents behave differently from target-specific ones

• Autoimmune research, where complexes of LL-37 with self-DNA are a studied mechanism

Conventional antibiotics inhibit specific proteins, and single mutations in those proteins confer resistance. An agent that disrupts membrane architecture presents a much harder target to evolve around, since the structure itself would have to change. That argument — not any single result — is what sustains the antimicrobial peptide field.

KPV covers the anti-inflammatory side of innate immunity, Thymosin Alpha-1 the adaptive side, and VIP the neuroimmune interface.