Product description
What is LL-37?
LL-37 is the only antimicrobial peptide from the cathelicidin family found in humans, consisting of 37 amino acids and beginning with two leucine residues (hence the name LL-37). The peptide sequence is LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES, and its full name is cathelicidin antimicrobial peptide (CAMP, Cathelicidin Antimicrobial Peptide).
LL-37 is produced as part of the innate immune system from a larger precursor - the hCAP18 protein (human Cationic Antimicrobial Protein 18 kDa). The precursor protein consists of a signal peptide, a cathelin-like domain, and a C-terminal LL-37 fragment. The mature LL-37 peptide is released by proteolytic cleavage by proteinase 3 in neutrophils or by serine proteases in keratinocytes.
Structurally, LL-37 is an amphipathic peptide - it has both cationic (positively charged) and hydrophobic regions. In aqueous solutions it adopts an α-helical structure, which is crucial for its biological activity. Its molecular mass is about 4493 Da. The positive net charge (+6) enables interactions with negatively charged bacterial membranes.
LL-37 is found in many cells, tissues, and body fluids, including neutrophils, macrophages, keratinocytes, epithelial cells of the respiratory and gastrointestinal tracts, as well as in sweat, breast milk, and seminal fluid. Expression of the peptide is regulated by vitamin D, linking vitamin D supplementation with antimicrobial immunity.
Mechanism of action
Antimicrobial action - LL-37 exhibits a broad spectrum of activity against Gram-positive and Gram-negative bacteria, fungi, viruses, and parasites. The mechanism involves binding to the negatively charged phospholipids of the microbial cell membrane, insertion into the lipid bilayer, and pore formation or membrane destabilization. Selectivity toward pathogens results from differences in the lipid composition of microbial membranes (more negatively charged lipids) compared with mammalian cells.
Anti-biofilm activity - LL-37 is capable of destroying preformed bacterial biofilms, which distinguishes it from many classic antibiotics. The peptide prevents biofilm formation by inhibiting bacterial adhesion and disrupting intercellular communication (quorum sensing). This activity is especially important in the context of infected chronic wounds.
Immunomodulation - In addition to direct bactericidal action, LL-37 modulates the immune response by: chemotaxis of neutrophils, monocytes, and T lymphocytes, activation of the P2X7 receptor and induction of IL-1β release, inhibition of macrophage activation by LPS through endotoxin neutralization, and stimulation of mast cell degranulation.
Promotion of wound healing - LL-37 supports wound healing by stimulating keratinocyte proliferation and migration, inducing angiogenesis through stimulation of endothelial cells, inhibiting keratinocyte apoptosis by increasing COX-2 expression, and promoting re-epithelialization in wound models.
Inhibition of apoptosis - Studies have shown that LL-37 protects keratinocytes from apoptosis induced by topoisomerase inhibitors. This effect is mediated by increased expression of cyclooxygenase-2 (COX-2), an enzyme involved in protection against cell death.
Scientific research directions
Research on LL-37 includes its potential applications in the treatment of antibiotic-resistant infections, chronic wounds, and as an immune adjuvant.
Infected chronic wounds
In the epithelium of chronic ulcers, a deficit of LL-37 is observed, whereas in normally healing wounds the peptide is strongly induced. In vivo studies have shown that topical application of synthetic and recombinant LL-37 increased vascularization and re-epithelialization of wounds in dexamethasone-treated mice. The peptide promoted proliferation, migration, and tubular structure formation by endothelial cells in vitro.
Diabetic ulcers and biofilms
Patients with diabetes often suffer from chronic lower-limb ulcers infected with multispecies bacterial biofilm. LL-37 shows both anti-biofilm activity against major pathogens (Pseudomonas, Staphylococcus) and wound-healing properties. The combination of these effects makes the peptide an attractive candidate for local therapy of infected diabetic wounds.
Development of analogs and derivatives
Due to high production costs, potential cytotoxicity at high concentrations, and proteolytic instability, intensive research is underway on modified LL-37 analogs. Strategies include: shortened analogs retaining activity (e.g., LL-37₁₇₋₂₉), retro-analogs with increased stability, D-amino acid modifications, and cyclic peptides. A 2025 study (Voronko et al.) summarizes key strategies for designing LL-37 analogs with improved functional properties.
Nanoparticle delivery systems
Nanoscale LL-37 delivery systems are being developed that enable targeted delivery, extend the peptide's half-life, and reduce cytotoxic effects. Research includes lipid nanoparticles, hydrogels, and functionalized electrospun membranes.
Scientific context
LL-37 belongs to the broader family of antimicrobial peptides (AMPs), which are an elemental component of the innate immune system of all multicellular organisms. Among human AMPs, the following can be mentioned:
- α and β defensins - small cysteine-rich peptides
- Histatins - antifungal peptides in saliva
- Dermcidin - a peptide present in sweat
- LL-37 - the only human cathelicidin
LL-37 stands out among AMPs for its multifunctionality - in addition to antimicrobial action, it performs immunomodulatory, chemotactic, and regenerative functions. This pleiotropic activity makes it an attractive candidate for a multifaceted therapeutic intervention.
The link between vitamin D and LL-37 expression has important clinical implications. Vitamin D deficiency, common in the population, correlates with reduced LL-37 expression and increased susceptibility to infections. Vitamin D supplementation increases LL-37 production, which may explain part of the health benefits attributed to this vitamin.
LL-37 also exhibits antiviral activity against enveloped viruses and is being studied in the context of respiratory viral infections. The peptide has also been the subject of research in the context of COVID-19 due to its potential antiviral and immunomodulatory effects.
Safety profile in studies
Overall tolerance - In preclinical studies and limited clinical studies, LL-37 has shown an acceptable safety profile at appropriate dosing. The peptide is a natural component of the human immune system, which suggests a favorable safety profile.
Cytotoxicity - At high concentrations (>25-50 μM), LL-37 may exhibit cytotoxicity toward mammalian cells, including erythrocytes (hemolysis) and keratinocytes. This effect results from nonspecific binding to cell membranes. Developed analogs aim to reduce cytotoxicity while preserving antimicrobial activity.
Pro-inflammatory effects - Paradoxically, LL-37 may in some contexts intensify inflammation through mast cell activation and the release of pro-inflammatory cytokines. The peptide is overexpressed in psoriasis, where it may contribute to disease pathogenesis through activation of dendritic cells.
Proteolytic stability - The main clinical limitation is the rapid degradation of LL-37 by proteases present in the wound environment and plasma. This requires the development of stabilized forms or delivery systems.
Regulatory status - LL-37 is not approved by the FDA or other major regulatory agencies as a drug. Clinical studies are underway evaluating topical preparations containing LL-37 or its analogs in the treatment of wounds and infections. The peptide is available for research purposes.
References – latest scientific studies
- Voronko OE et al. Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37 and Its Modifications. Int J Mol Sci. 2025;26(16):8103. PubMed
- Bhattacharjya S et al. LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases. Biomolecules. 2024;14(3):320. PMC
- Ramos R et al. Wound healing activity of the human antimicrobial peptide LL37. Peptides. 2011;32(7):1469-1476. PubMed
- van Hoek ML. The Human Cathelicidin Antimicrobial Peptide LL-37 as a Potential Treatment for Polymicrobial Infected Wounds. Front Immunol. 2013;4:143. PMC
- Heilborn JD et al. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol. 2003;120(3):379-389. PubMed
- Bandurska K et al. Unique features of human cathelicidin LL-37. Biofactors. 2015;41(5):289-300. PubMed
- Nagaoka I et al. Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. J Immunol. 2001;167(6):3329-3338. PubMed
- Tokumaru S et al. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J Immunol. 2005;175(7):4662-4668. PubMed
- Overhage J et al. Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun. 2008;76(9):4176-4182. PMC
- Wang G et al. Design of Antimicrobial Peptides: Progress Made with Human Cathelicidin LL-37. Adv Exp Med Biol. 2019;1117:215-240. PubMed
