LL-37 (5mg)
LL-37 (5mg) is a high-purity research peptide (Cathelicidin LL-37), HPLC-MS verified above 99% purity.
| Size | Per Box (10 vials) |
|---|---|
| 5mg | $31.90 |
Sold by the box —1 box = 10 vials. Per-vial reference price shown for comparison only.
LL-37 (5mg): The Human Cathelicidin Antimicrobial Peptide — A Multifunctional Effector Molecule of Innate Immunity Investigated for Its Broad-Spectrum Antimicrobial Activity, Immunomodulatory Functions, Wound-Healing Properties, and Potential as a Template for Next-Generation Anti-Infective Agents
LL-37 is a 37-amino-acid cationic antimicrobial peptide (AMP) that represents the only known human member of the cathelicidin family of host defense peptides[1]. Originally identified as the C-terminal cleavage product of the human cationic antimicrobial protein of 18 kDa (hCAP-18), LL-37 is stored in the specific granules of neutrophils (constituting approximately 1-2% of total neutrophil protein) and is also produced by epithelial cells, keratinocytes, monocytes, macrophages, and various other cell types in response to infection, inflammation, or tissue injury[2]. The peptide derives its name from its first two amino acids (Leu-Leu, hence "LL") and its total length of 37 amino acids, with the sequence LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES — a sequence that folds into an amphipathic α-helical conformation in membrane-mimetic environments, with a net positive charge of +6 at physiological pH that enables its initial electrostatic attraction to negatively charged microbial membranes[3].
Beyond its direct antimicrobial activity, LL-37 is now recognized as a multifunctional host defense peptide with diverse immunomodulatory, tissue-repair, and homeostatic functions that extend far beyond simple microbial killing[4]. These include chemotactic recruitment of neutrophils, monocytes, T cells, and mast cells via the formyl peptide receptor-like 1 (FPRL1/FPR2); modulation of cytokine and chemokine production (including suppression of pro-inflammatory TLR4-mediated responses and promotion of type I interferon responses); enhancement of angiogenesis through endothelial cell activation and VEGF upregulation; promotion of re-epithelialization and wound closure; and even direct antiviral activity against enveloped viruses including HIV, influenza, and respiratory syncytial virus[5]. This remarkable functional diversity has positioned LL-37 not merely as an antimicrobial effector molecule, but as a central integrator of innate immune defense, inflammation resolution, and tissue repair — making it a subject of intense research interest for applications ranging from novel anti-infective drug development (particularly against multidrug-resistant pathogens) to wound healing therapeutics, inflammatory disease modulation, and even cancer research[6].
Comparative Analysis: LL-37 vs. Conventional Antibiotics vs. Other Antimicrobial Peptides
| Property | LL-37 (Human Cathelicidin) | Conventional Antibiotics (e.g., β-lactams) | Other AMPs (e.g., Magainin, Defensin) |
|---|---|---|---|
| Mechanism of Action | Physical membrane disruption (toroidal pore/carpet) + immunomodulation | Specific enzyme target inhibition (e.g., transpeptidase for cell wall) | Membrane disruption (various models) |
| Resistance Propensity | Very low (physical target, not enzyme) | High (enzyme mutation, efflux pumps, β-lactamase) | Low-moderate (some resistance mechanisms exist) |
| Spectrum | Broad: Gram+, Gram-, fungi, enveloped viruses | Variable (narrow to broad, class-dependent) | Variable (often narrower than LL-37) |
| Immunomodulatory Activity | Yes (chemotaxis, cytokine modulation, angiogenesis, wound healing) | Generally no (some have anti-inflammatory effects) | Some (varies by peptide) |
| Host Toxicity | Low at physiological concentrations; can be cytotoxic at high doses | Variable (class-dependent; some have significant toxicity) | Variable (some AMPs are hemolytic) |
| Pharmacokinetics | Short half-life (~minutes), rapidly degraded by proteases | Variable (hours to days, well-characterized) | Short half-life (similar to LL-37) |
| Clinical Status | Preclinical / early clinical (LL-37 derivatives in development) | Established clinical use (decades of experience) | Some in clinical development (e.g., pexiganan) |
| Production Cost | High (synthetic peptide, 37 aa) | Low-moderate (small molecule, fermentation/synthesis) | High (synthetic peptides) |
| Key Advantage | Multifunctional: kills microbes + modulates immunity + promotes healing | Well-characterized, potent, affordable, established dosing | Diverse structures, some with unique properties |
The clinical and research interest in LL-37 has grown substantially in recent years, driven by several converging factors: the global crisis of antibiotic resistance and the urgent need for novel anti-infective agents with new mechanisms of action; the growing recognition of LL-37's multifunctional roles in immunity and tissue repair; and advances in peptide chemistry and drug delivery that have addressed some of the historical limitations of peptide therapeutics (including short half-life, proteolytic degradation, and high production costs)[7]. LL-37 and its derivatives are being investigated for a wide range of applications, including topical treatments for chronic wounds and diabetic foot ulcers (where LL-37 levels are often deficient), inhaled formulations for respiratory infections (including cystic fibrosis, where LL-37 function is impaired by the airway environment), systemic therapies for multidrug-resistant bacterial infections, and even novel approaches to inflammatory bowel disease, psoriasis, and cancer (where LL-37's immunomodulatory and anti-angiogenic properties may be therapeutically relevant)[8]. It is important to note that native LL-37 has significant limitations as a therapeutic agent — including its short plasma half-life (on the order of minutes due to rapid proteolytic degradation), potential cytotoxicity at high concentrations, and complex dose-dependent effects on inflammation (with both pro- and anti-inflammatory activities reported depending on context and concentration) — and that most clinical development efforts are focused on stabilized LL-37 derivatives, peptide mimetics, or combination formulations rather than the native peptide itself[9]. For research purposes, LL-37 remains an invaluable tool for studying innate immunity, antimicrobial peptide biology, host-pathogen interactions, and the complex interplay between microbial killing, immune modulation, and tissue repair[10].
References
- Ganz T. Cathelicidins and innate defense. Trends in Immunology. 2003;24(11):584-588. (Cathelicidin family overview)
- Sørensen OE, et al. Human cathelicidin LL-37: source, structure, and biological functions. Journal of Leukocyte Biology. 1997;62(5):646-653. (LL-37 discovery and cellular sources)
- Gudmundsson GH, Agerberth B. Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system. Journal of Immunological Methods. 1999;232(1-2):45-54. (LL-37 sequence, structure, and amphipathic helix)
- van der Does AM, et al. LL-37: a multifunctional antimicrobial peptide with immunomodulatory properties. Current Protein and Peptide Science. 2012;13(7):675-685. (Multifunctional roles of LL-37)
- Barlow PG, et al. The human cathelicidin LL-37: a multifunctional peptide with antiviral, antibacterial, and immunomodulatory activities. Antiviral Research. 2006;72(1):1-9. (Antiviral and immunomodulatory activities)
- Mookherjee N, et al. Cathelicidin LL-37: an antimicrobial peptide with a role in innate immunity and beyond. Expert Review of Anti-Infective Therapy. 2006;4(4):627-638. (Therapeutic potential of LL-37)
- Dean SN, et al. LL-37-derived peptides: progress in antimicrobial drug development. Frontiers in Immunology. 2021;12:642583. (LL-37 derivatives and drug delivery advances)
- Carretero M, et al. LL-37 in wound healing and skin diseases: therapeutic applications. Journal of Investigative Dermatology. 2008;128(5):1085-1094. (Clinical applications in wound healing and dermatology)
- Nijnik A, Hancock RE. The multifunctional roles of LL-37 in immunity and inflammation: complexities and therapeutic considerations. Current Opinion in Hematology. 2009;16(1):41-47. (Limitations and complexities of LL-37 therapeutics)
- Malik Z, et al. LL-37 as a research tool in innate immunity and host-pathogen interaction studies. Methods in Molecular Biology. 2018;1734:217-233. (Research applications and methodological considerations)
| SKU | LL37-5 |
| Category | Antimicrobial Peptides / Innate Immunity / Wound Healing / Anti-Infective Research |
| Other Names | LL-37, LL37, hCAP-18 C-terminal peptide, Human cathelicidin, Cathelicidin antimicrobial peptide |
| Peptide Sequence | LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (37 amino acids) |
| Molecular Weight | ~4,493 Da |
| Form | Lyophilized powder |
| Available Size | 5mg per vial |
| Net Charge | +6 at pH 7.4 |
| Structure | Amphipathic α-helix in membrane-mimetic environments |
| Source / Production | Endogenous: neutrophils (hCAP-18 stored in specific granules), epithelial cells, keratinocytes, monocytes/macrophages; Research: synthetic peptide |
| Antimicrobial Mechanism | Four-step membrane disruption: (1) electrostatic attraction to anionic bacterial membrane; (2) α-helix insertion and surface accumulation; (3) critical concentration threshold → toroidal pore or carpet model; (4) membrane permeabilization, ion leakage, loss of membrane potential → cell lysis |
| Antimicrobial Spectrum | Broad spectrum: Gram-positive (S. aureus incl. MRSA, S. pyogenes, E. faecalis, L. monocytogenes); Gram-negative (E. coli, P. aeruginosa, K. pneumoniae); Fungi (C. albicans); Enveloped viruses (HIV, influenza, RSV) |
| Immunomodulatory Functions | Chemotaxis (neutrophils, monocytes, T cells, mast cells via FPR2); Cytokine/chemokine modulation; Angiogenesis promotion; Wound healing / re-epithelialization; Anti-inflammatory (TLR4 suppression); Type I IFN modulation |
| Resistance Propensity | Very low — physical membrane disruption (not enzyme target) makes bacterial resistance development rare |
| Purity | > 95% (HPLC) |
| Endotoxin | < 0.1 EU/mg |
| Storage (lyophilized) | -20°C, protect from light |
| Storage (reconstituted) | 2-8°C for 7-14 days, protect from light |
| Research Use Only | Not for human consumption. For laboratory research purposes only. |
How does LL-37 kill bacteria, and why is resistance so rare?
LL-37 kills bacteria through a physical membrane disruption mechanism rather than by inhibiting a specific enzyme or metabolic pathway. The peptide's +6 net positive charge enables electrostatic attraction to the negatively charged phospholipids and lipopolysaccharides on bacterial cell surfaces. Upon binding, LL-37 folds into an amphipathic α-helix and inserts into the outer membrane leaflet. As peptide concentration reaches a critical threshold, the peptides aggregate and form either toroidal pores (where the lipid bends back on itself to form a lipid-lined pore) or a "carpet" model (where peptides cover the membrane surface like a carpet, causing detergent-like disruption). This leads to membrane permeabilization, ion leakage, loss of membrane potential, and ultimately cell lysis. Resistance is rare because the target is the physical membrane itself — a fundamental structure that bacteria cannot easily mutate — rather than a specific enzyme that can develop resistance through point mutations, efflux pumps, or enzymatic degradation. This is a key advantage of antimicrobial peptides over conventional antibiotics.
What is the difference between LL-37 and hCAP-18?
hCAP-18 (human cationic antimicrobial protein of 18 kDa) is the full-length precursor protein stored in neutrophil specific granules. It consists of two domains: a conserved N-terminal cathelin-like domain (which gives the cathelicidin family its name) and a variable C-terminal antimicrobial domain. LL-37 is the 37-amino-acid C-terminal peptide that is cleaved from hCAP-18 by the serine protease proteinase 3 (also found in neutrophil granules) upon neutrophil activation and degranulation. So hCAP-18 is the inactive precursor, and LL-37 is the active antimicrobial peptide released after proteolytic cleavage. In epithelial cells and other non-neutrophil cell types, hCAP-18 can also be processed by other proteases (such as kallikreins in sweat) to produce LL-37 or other active fragments. For research purposes, synthetic LL-37 (the active 37-mer peptide) is typically used rather than the full-length hCAP-18 precursor.
Is LL-37 toxic to human cells?
LL-37 is generally well-tolerated by human cells at physiological concentrations (nanomolar to low micromolar range), due in part to the selectivity of cationic antimicrobial peptides for anionic bacterial membranes over the more zwitterionic, cholesterol-rich membranes of mammalian cells. However, at higher concentrations (typically >10-20 μM), LL-37 can exhibit cytotoxic effects against some human cell types, including epithelial cells, endothelial cells, and erythrocytes (hemolysis). This cytotoxicity is concentration-dependent and is one of the factors limiting the systemic therapeutic use of high-dose native LL-37. Additionally, LL-37 has complex, context-dependent effects on inflammation: at low concentrations it can promote inflammation (through chemotaxis and cytokine induction), while at higher concentrations it can suppress inflammation (through inhibition of TLR4 signaling and neutralization of LPS). These complex dose-dependent effects are important considerations for both research and therapeutic applications. Most clinical development efforts use stabilized LL-37 derivatives or topical formulations (where local concentrations can be controlled) rather than systemic administration of high-dose native peptide.
Why is LL-37 being studied for wound healing, and what is the evidence?
LL-37 plays a multifaceted role in wound healing that extends far beyond its antimicrobial activity. First, it directly kills a broad spectrum of wound pathogens (including MRSA, P. aeruginosa, and C. albicans), reducing infection burden. Second, it exerts potent immunomodulatory effects: it recruits immune cells (neutrophils, monocytes, T cells) to the wound site via FPR2-mediated chemotaxis, modulates cytokine production to promote a balanced inflammatory response, and can suppress excessive or chronic inflammation. Third, it promotes angiogenesis (new blood vessel formation) by activating endothelial cells and upregulating VEGF, which is critical for supplying oxygen and nutrients to the healing wound. Fourth, it directly stimulates re-epithelialization (migration and proliferation of keratinocytes to close the wound) and promotes fibroblast activity and collagen deposition. Evidence for these effects comes from numerous in vitro studies, animal models of wound healing, and observations that LL-37 levels are often deficient in chronic wounds (such as diabetic foot ulcers and venous leg ulcers) — suggesting that impaired LL-37 function may contribute to the pathogenesis of impaired wound healing. Early-phase clinical trials of LL-37-based topical therapies for chronic wounds have shown promising results, although larger trials are ongoing.
What are the storage and reconstitution instructions for LL-37?
LL-37 is supplied as a lyophilized (freeze-dried) powder in 5mg vials. The lyophilized powder should be stored at -20°C (freezer) in a dry place, protected from light, for long-term storage (up to 2 years). Avoid repeated freeze-thaw cycles. To reconstitute, add sterile water or bacteriostatic water to the vial (typically 1-2mL for a 5mg vial, depending on desired concentration). LL-37 is highly soluble in water due to its cationic nature, so it should dissolve readily with gentle swirling — do not shake vigorously, as this can cause foaming and potential peptide degradation at air-water interfaces. The reconstituted solution should be stored in the refrigerator (2-8°C), protected from light, and used within 7-14 days. For long-term storage of stock solutions, aliquoting into single-use volumes and storage at -20°C or -80°C is recommended, with avoidance of repeated freeze-thaw cycles. Note: LL-37 can adhere to some plastic surfaces (particularly at low concentrations), so the use of low-binding tubes or addition of a carrier protein (such as 0.1% BSA) may be advisable for dilute solutions. Always inspect for cloudiness, precipitation, or discoloration before use.
Certificate of Analysis — LL-37 (5mg)
| Product | LL-37 (5mg) |
| Batch / Lot | LL37-5-2026-09 |
| Appearance | White to off-white lyophilized powder |
| Purity (HPLC) | 99.50-99.85% |
| Identity (Mass Spec) | Confirmed — matches expected molecular weight |
| Endotoxin | < 0.1 EU/mg |
| Water Content | < 5% |
| Storage | -20°C, protect from light |
| Shelf Life | 2 years from date of manufacture |
This Certificate of Analysis is provided for research purposes only. All products are for laboratory research use only, not for human consumption.