LL-37

Description

LL-37 is the only cathelicidin-derived antimicrobial peptide found in humans. Produced by neutrophils, macrophages, and epithelial cells, this 37-amino acid peptide serves as a frontline component of innate immune defense. Its name comes from the two leucine residues at its N-terminus.

Research Profile

LL-37 disrupts microbial membranes through electrostatic interaction with negatively charged phospholipid bilayers — a mechanism that makes bacterial resistance development difficult. Beyond direct antimicrobial action, research published in Nature Reviews Immunology and the Journal of Immunology describes LL-37’s immunomodulatory properties: chemotaxis of immune cells, modulation of inflammatory cytokines, and promotion of wound closure through keratinocyte migration.

Key Research Areas

• Broad-spectrum antimicrobial activity (gram-positive, gram-negative, fungi)
• Biofilm disruption and prevention
• Immune cell recruitment and modulation
• Wound healing acceleration
• Anti-inflammatory signaling in sepsis models

Specifications

Amino Acids	37 residues
Molecular Weight	4493.33 g/mol
Purity	≥99% (HPLC verified)
Form	Lyophilized powder
Quantity	5mg per vial
Storage	-20°C pre-reconstitution

Related Research Peptides

LL-37 pairs with Thymosin Alpha 1 in immune research and with KPV and BPC-157 in inflammation studies. See our guides on peptides for immune support and peptides for healing.

Research Dosage Protocols

LL-37 research uses dose ranges that vary significantly by application. Antimicrobial studies in vitro typically test minimum inhibitory concentrations (MICs) between 1–16µg/mL against target organisms. In vivo animal infection models use subcutaneous or intraperitoneal doses of 0.5–5mg/kg, with some wound healing models using topical application at 10–100µg/mL in gel carriers. A 5mg vial reconstituted in 1mL bacteriostatic water yields 5,000µg/mL, which should be diluted to working concentrations for most protocols. LL-37 is light-sensitive and prone to aggregation at high concentrations — keep solutions dilute and shielded from UV exposure.

Frequently Asked Questions

How does LL-37 disrupt bacterial biofilms?

Biofilm disruption by LL-37 involves two mechanisms: electrostatic membrane disruption and interference with quorum sensing. LL-37’s cationic, amphipathic helix structure is attracted to the negatively charged lipopolysaccharide matrix of bacterial biofilms. It inserts into bacterial membranes, forming pores or causing membrane dissolution. Beyond direct killing, research shows LL-37 inhibits biofilm formation by binding to extracellular DNA (a structural component of biofilm matrix) and interfering with the c-di-GMP signaling that bacteria use to coordinate biofilm development. This dual mechanism makes it relevant to research on chronic infections where conventional antibiotics fail at biofilm penetration.

Does LL-37 work against both gram-positive and gram-negative bacteria?

Yes — LL-37 shows activity against both gram-positive and gram-negative bacteria, as well as fungi and some enveloped viruses, which classifies it as a broad-spectrum host defense peptide. Its cationic charge interacts with lipoteichoic acid in gram-positive cell walls and lipopolysaccharide (LPS) in gram-negative outer membranes. The MIC values vary by organism; gram-negative bacteria like Pseudomonas aeruginosa and E. coli have been studied extensively. LL-37 also neutralizes free LPS, which is relevant for sepsis research — it prevents the systemic inflammatory cascade triggered by circulating bacterial membrane components.

Why is LL-37 particularly sensitive to storage conditions?

Why is LL-37 particularly sensitive to storage conditions?

LL-37 is a 37-amino acid peptide with a strong tendency to aggregate — its amphipathic helix structure (hydrophilic one side, hydrophobic the other) causes peptide chains to cluster at elevated concentrations or temperatures. Aggregation reduces bioactivity because the antimicrobial mechanism requires the peptide to be in monomeric or small oligomeric form to insert into bacterial membranes. Light accelerates oxidative degradation of tryptophan residues in the sequence. Best practice: store lyophilized at -80°C for long-term, reconstitute in dilute acetic acid or sterile water immediately before use, and avoid freeze-thaw cycling with reconstituted solutions.

How does LL-37 differ from traditional antibiotics mechanistically?

Traditional antibiotics typically target specific bacterial proteins — cell wall synthesis enzymes, ribosomes, DNA gyrase. This specificity is why resistance develops: a single mutation in the target protein can render the antibiotic ineffective. LL-37 attacks bacterial membranes directly through physical disruption rather than enzymatic target binding. Because resistance would require bacteria to fundamentally restructure their membrane lipid composition (an extremely high evolutionary cost), resistance development to LL-37 is rare and slow. Additionally, LL-37 does this while simultaneously modulating the host immune response — a dual function no conventional antibiotic replicates.

What immune modulation effects beyond antimicrobial activity has LL-37 research documented?

LL-37 functions as a genuine immunomodulatory peptide beyond its direct antimicrobial activity. Research documents: recruitment of monocytes, neutrophils, and T cells to infection sites via chemotactic signaling; promotion of dendritic cell maturation; enhancement of phagocytic clearance by macrophages; and suppression of excessive LPS-induced TNF-α production (an anti-inflammatory effect that paradoxically coexists with its pro-inflammatory recruitment role). This context-dependent immunomodulation is studied in wound healing, autoimmune, and cancer biology research — LL-37 is elevated in several cancers and may play a role in angiogenesis and cancer cell migration.

What research dosing approaches have been used in wound healing models?

Wound healing research with LL-37 has used both topical and subcutaneous delivery. Topical formulations in published studies typically deliver 5–50µg per wound site in gel or saline carriers. Subcutaneous peri-wound injection uses 0.1–1mg/kg doses. Studies show that LL-37 accelerates keratinocyte migration (re-epithelialization), promotes granulation tissue formation, and enhances angiogenesis through VEGF signaling at the wound site. The peptide’s dual role — clearing potential infection while simultaneously stimulating repair — makes it a compelling subject for chronic wound research, particularly diabetic wound models where both infection risk and impaired healing converge.

For research and laboratory use only. Not for human consumption. All peptides are sold strictly as research chemicals.