LL-37 is the only cathelicidin-family host-defence peptide found in humans: a 37-residue, cationic, amphipathic alpha helix released from the C-terminus of the precursor protein hCAP18, and the single most studied antimicrobial peptide in human innate immunity research. Its name is literal — two leading leucines and 37 residues. At 4493.33 g/mol it is by far the largest peptide in this catalogue's anti-inflammatory group, and its size, charge and helical character determine both its reported mechanisms and the practical difficulty of synthesising and handling it.
This page sets out the origin of the sequence, the structural features that drive its behaviour, the mechanisms reported in the literature, the research areas where it appears, and the laboratory specifics of the material. LL-37 is supplied as a lyophilized powder for laboratory research use only.
LL-37 at a glance
| Property | Value |
|---|---|
| Sequence | LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES |
| Length | 37 residues |
| Precursor | hCAP18, product of the CAMP gene |
| Releasing enzyme | Proteinase 3 (neutrophil serine protease) |
| CAS number | 154947-66-7 |
| Molecular weight | 4493.33 g/mol |
| Structure in solution | Largely unstructured in water; alpha-helical on anionic membranes |
| Net charge | Strongly cationic at physiological pH |
| Family | Cathelicidin — the sole human member |
| Physical form | Lyophilized powder, sealed glass vial |
| Sizes supplied | 5 mg, 10 mg |
| Purity specification | ≥99% by RP-HPLC with mass confirmation |
Origin and structure: from hCAP18 to a 37-residue helix
Cathelicidins are defined by a conserved N-terminal cathelin domain attached to a highly variable C-terminal antimicrobial region. Most mammals carry several; humans carry exactly one gene, CAMP, whose product is the 18 kDa protein hCAP18. The protein is stored in the specific granules of neutrophils and is also expressed by keratinocytes, epithelial cells of the airway and gut, and several other cell types. Proteolytic cleavage — principally by proteinase 3 in neutrophils, and by other proteases such as kallikreins in skin — liberates the C-terminal 37 residues as the mature cathelicidin peptide.
Structurally the peptide is a textbook amphipathic helix. In dilute aqueous buffer it is largely disordered, but on contact with an anionic surface it folds into a helix in which basic residues (arginine and lysine) cluster on one face and hydrophobic residues on the other. That segregation is the whole mechanism in miniature: the cationic face provides electrostatic attraction to negatively charged bacterial membranes, and the hydrophobic face inserts into the lipid interior.
The same properties make LL-37 an awkward molecule to produce and to handle. Thirty-seven residues is a long solid-phase synthesis; the hydrophobic stretch is prone to on-resin aggregation; and the finished peptide adsorbs readily to plastic and glass surfaces. Its price relative to short sequences reflects this, and so does the need for careful handling once it is in solution.
How LL-37 is thought to work
Two mechanistic accounts run in parallel through the literature, and they are not in competition.
Direct membrane interaction
The classical description is electrostatic association with the anionic phospholipids and lipopolysaccharide of bacterial envelopes, followed by helix insertion and loss of membrane integrity. Models proposed include carpet-like surface disruption and toroidal pore formation, and different studies favour different geometries depending on lipid composition and peptide concentration. Because the mechanism is physicochemical rather than target-specific, it is often discussed as less prone to conventional resistance development than enzyme-directed antibiotics — a hypothesis frequently stated in reviews rather than a demonstrated property. Mammalian membranes, being far less anionic on their outer leaflet, are much less susceptible, which is the basis of the selectivity argument.
Immunomodulation
The second body of work describes LL-37 as a signalling molecule rather than a membrane-active agent. Reported activities include chemotactic recruitment of neutrophils, monocytes and T cells through formyl peptide receptor-like 1, neutralisation of lipopolysaccharide and dampening of the resulting inflammatory cascade, modulation of toll-like receptor responses, and effects on keratinocyte migration and angiogenesis in wound models. At the concentrations reachable in most tissues, several authors argue that the immunomodulatory role is the physiologically dominant one and direct membrane activity is secondary.
A third and important observation is context dependence. LL-37 forms complexes with self-DNA and RNA that can drive interferon responses, work that connects the peptide to research on autoinflammatory skin conditions. The same molecule that is described as protective in one model is described as a driver of pathology in another, which is a strong argument for reading LL-37 results in the specific context of the model used.
What research has examined
Antimicrobial and antibiofilm assays
Minimum inhibitory concentration determinations against Gram-positive and Gram-negative organisms, membrane permeabilisation assays and biofilm prevention and dispersal studies form the largest block of published in-vitro work. A recurring methodological finding is strong dependence on assay salt concentration and serum content, since divalent cations and serum proteins compete for the peptide's cationic face.
Wound and skin models
Cell and rodent work has examined re-epithelialisation, keratinocyte migration and vascular responses, alongside investigation of altered cathelicidin expression in skin conditions.
Innate immune signalling
Studies on chemotaxis, LPS neutralisation, macrophage phenotype and interferon induction sit here. This is where LL-37 is most often compared with other immune-directed research peptides such as thymosin alpha-1; the two are frequently confused as interchangeable immune peptides when their mechanisms are entirely different, a contrast covered in LL-37 vs thymosin alpha-1.
Formulation and delivery research
Because the peptide adsorbs to surfaces and is protease-sensitive, a substantial applied literature examines truncated analogues, D-amino-acid variants and delivery vehicles intended to retain activity with less material.
All of this is laboratory and preclinical work. LL-37 has no approved use, and human data are limited to early-stage investigation of derived analogues rather than the native sequence as sold for research.
Forms and sizes we supply
LL-37 is stocked as a lyophilized powder in 5 mg (USD 115) and 10 mg (USD 195) sealed vials. The molar arithmetic is unforgiving compared with short peptides: at 4493.33 g/mol, a 5 mg vial contains only about 1.1 micromoles, roughly one-thirteenth the molar quantity of a 5 mg vial of a tripeptide. Assays that call for micromolar working concentrations in reasonable volumes consume material quickly, which is the practical reason the 10 mg size exists. Related material sits under anti-inflammatory peptides and immune peptides; purchasing considerations are covered in our LL-37 buying guide.
Reconstitution and storage in a laboratory context
The calculation is straightforward: a 5 mg vial reconstituted with 1 mL of diluent gives 5 mg/mL, equivalently 5,000 mcg/mL, and in molar terms approximately 1.11 mM. Because published assay concentrations are usually in the low micromolar range, most work involves dilutions of several hundred-fold.
Three handling points are specific to this peptide. First, surface adsorption is real and measurable; low-binding tubes and pipette tips are standard practice, and glass is generally preferred over untreated polypropylene for stock solutions. Second, buffer ionic strength changes apparent activity, so the diluent must be recorded as part of the method rather than treated as incidental. Third, the long hydrophobic stretch makes aggregation a genuine risk: add diluent slowly down the vial wall, swirl rather than shake, and inspect the solution against light for haze before use. Lyophilized vials are stored at −20 °C or colder, protected from light and moisture; reconstituted solution is aliquoted and kept cold so that a single container is not warmed and re-chilled repeatedly. Detail is in the peptide storage guide.
Purity, COA and how to read one
Each lot is purified by reversed-phase HPLC to at least 99% with mass confirmation and a lot-matched certificate. For a peptide of this length the certificate carries more information than usual, and it is worth reading properly. Deletion sequences — chains missing one residue — are the characteristic impurity of long syntheses, and a peptide missing a single alanine differs by only 71 Da from the full-length product, so both the mass spectrum and the chromatographic resolution matter. Look for a single dominant peak with good symmetry rather than a broad envelope. Net peptide content is also more consequential here than for short sequences: with a strongly basic peptide supplied as a TFA salt, counter-ion and residual water can account for a substantial share of gross vial weight, which matters directly if molar concentrations are being reported. Our guide to reading a peptide COA works through these checks on real documents.
Regulatory status
LL-37 is an endogenous human peptide, but the synthetic material supplied here is not an approved drug, a dietary supplement or a compounded preparation. It is research use only, for in-vitro and preclinical laboratory investigation by qualified researchers, and is not intended for human or veterinary administration. No therapeutic claim is made for it, and none of the published antimicrobial or immunomodulatory findings should be read as evidence of clinical utility.
Related peptides and further reading
For immune-directed research more broadly, see the peptides for immune support research overview. Thymosin alpha-1 and KPV occupy adjacent but mechanistically distinct positions in the same catalogue, and the institutional research listings group host-defence material under the LL-37 family.