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LL-37

Also identified as Cathelicidin antimicrobial peptide LL-37, hCAP-18 fragment

Cathelicidin antimicrobial peptide fragment

Sequence: Leu-Leu-Gly-Asp-Phe-Phe-Arg-Lys-Ser-Lys-Glu-Lys-Ile-Gly-Lys-Glu-Phe-Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg-Asn-Leu-Val-Pro-Arg-Thr-Glu-Ser

Molecular weight
4493
Molecular formula
C205H340N60O53
CAS
154947-66-7
Published studies reviewed
6

FOR RESEARCH USE ONLY. NOT FOR HUMAN OR VETERINARY USE. NOT FOR HUMAN CONSUMPTION.

Compounds described on this site are supplied solely for laboratory research. They are not offered for human or veterinary use or for clinical use, and they are not intended to diagnose, mitigate, cure or prevent any disease.

LL-37 is a 37-residue peptide corresponding to residues 134 to 170 of the human cathelicidin precursor hCAP-18, named for its two leading leucines and its length. The six publications reviewed include four laboratory studies of the gene, its cleavage from the precursor and its structure on model membranes, plus one randomised placebo-controlled study in 34 participants with leg ulcers and a single-person case report. The human record is small, and engineered relatives such as KR-12, like studies of the body's own cathelicidin, are excluded.

At a glance

Also identified as
Cathelicidin antimicrobial peptide LL-37, hCAP-18 fragment
Class
Cathelicidin antimicrobial peptide fragment
Target or mechanism
Phospholipid membranes (bacterial and mammalian, in model systems)
Evidence types represented
in vitro, human
Published studies reviewed
6
Last reviewed
2026-09-21

Overview

LL-37 is a 37-residue peptide: residues 134 to 170 of the human cathelicidin precursor protein hCAP-18 (UniProt P49913). Its name records its first two residues, both leucine, and its length.

The publications on this page are of three kinds. Two describe where the peptide comes from — the gene, and the enzyme that cuts the mature peptide out of its precursor. Two are structural: they describe how the peptide is arranged when it binds a model membrane, and report that the same material acts on bacterial and on ordinary mammalian membranes rather than selectively on one.

The human record is small and is printed here in full: one randomised, placebo-controlled study of the peptide in 34 participants with venous leg ulcers, and one report of skin findings in a single person taking part in a phase 1 melanoma study.

Not recorded on this page: hCAP-18 as a whole protein, engineered relatives such as KR-12, OP-145 or SE-33, and the large literature on how much cathelicidin the body itself makes. Those measure a different molecule, or measure the body rather than the material.

Mechanism under investigation

LL-37
  • Phospholipid membranes (bacterial and mammalian, in model systems)

The two structural studies recorded here describe LL-37 bound to model membranes and micelles: an amphipathic helix that lies along the membrane surface rather than spanning it, which their authors read as a detergent-like, carpet-type interaction rather than the formation of a pore. One of them also reports the peptide is cytotoxic in vitro to bacterial and to ordinary eukaryotic cells alike. No source on this page identifies a receptor.

Scope of the published work

Areas investigated
  • Gene and precursor processing
  • Membrane structure and interaction
  • Antibacterial activity in vitro
  • Venous leg ulcers
  • Skin adverse events
Models used
  • Human granulocyte preparations
  • Model lipid membranes and micelles
  • Randomised human study
  • Single-person case report

Every human figure on this page was recorded in a controlled study, under supervision, using material prepared for that study, in a population selected by its entry criteria. It is not the research material PepGenex supplies and no result here transfers to it.

Limitations

Evidence represented on this page: in vitro and human. No animal research is represented. The page reviews 6 published studies, and each figure is reported for the study that published it; results are not pooled across studies.

Common questions

What is LL-37?

LL-37 is a 37-residue peptide: residues 134 to 170 of the human cathelicidin precursor protein hCAP-18 (UniProt P49913).

How does LL-37 work, according to the published research?

The two structural studies recorded here describe LL-37 bound to model membranes and micelles: an amphipathic helix that lies along the membrane surface rather than spanning it, which their authors read as a detergent-like, carpet-type interaction rather than the formation of a pore. One of them also reports the peptide is cytotoxic in vitro to bacterial and to ordinary eukaryotic cells alike. No source on this page identifies a receptor.

  • Determined the three-dimensional structure of LL-37 in dodecylphosphocholine micelles by NMR, the peptide having been incorporated into the micelles for the measurement. Under those conditions the peptide adopts a helix-break-helix conformation with both termini unstructured and solvent-exposed; the N-terminal helical region is the more dynamic and the C-terminal helix the more structured and solvent-protected. The break between the helices sits at K12 and is described as probably stabilised by a hydrophobic cluster of I13, F17 and I20 together with a salt bridge between K12 and E16. The peptide is adsorbed on the micelle surface, its hydrophilic face toward the water and its hydrophobic face buried in the micelle. (Porcelli et al., 2008, PMID 18439024)
  • Reports that the precursor hCAP-18 showed no detectable cleavage inside cells after phagocytosis, but was cleaved to LL-37 in exocytosed material, and that of the three known serine proteases of azurophil granules, proteinase 3 was solely responsible for that cleavage. The authors describe this as the first detailed account of how this human peptide is generated from its precursor protein. (Sørensen et al., 2001, PMID 11389039)
  • Reports that in vitro the peptide is cytotoxic to bacterial and to ordinary eukaryotic cells alike. Polarised attenuated total reflectance Fourier-transform infrared spectroscopy found it predominantly α-helical and oriented nearly parallel to the surface of zwitterionic membranes, which the authors state does not support a channel-forming model but rather a detergent-like, carpet-type interaction. (Oren et al., 1999, PMID 10417311)

What has published research on LL-37 found, and what are its limits?

This page records 6 publications, reporting laboratory (in vitro) work in 4, human work in 2. Each is listed with its identifier under References.

Human studies represented: Grönberg et al., 2014, PMID 25041740; Dolkar et al., 2018, PMID 29665030.

Evidence represented on this page: in vitro and human.

No animal research is represented.

The page reviews 6 published studies, and each figure is reported for the study that published it; results are not pooled across studies.

Every human figure on this page was recorded in a controlled study, under supervision, using material prepared for that study, in a population selected by its entry criteria. It is not the research material PepGenex supplies and no result here transfers to it.

Is LL-37 approved by the U.S. FDA?

This page cites no FDA approval record for LL-37; PepGenex Science states a U.S. regulatory status only where a sourced record exists.

PepGenex research materials are not FDA approved and are not for human or veterinary use.

What risks have published studies of LL-37 reported?

2 published human studies on this page report adverse events or safety measurements. Each is listed with its publication in the adverse-events section of this page.

Trial events do not establish a complete safety profile.

What adverse events have been reported in published studies of LL-37?

Adverse events and safety measurements as reported by the published human studies on this page. Each entry is attributed to its publication.

Grönberg et al., 2014, PMID 25041740

Design and population
A first-in-man, randomised, double-blind, placebo-controlled study of the synthetic human peptide, in 34 participants with hard-to-heal venous leg ulcers. It comprised a 3-week open-label run-in period on placebo, a 4-week randomised double-blind phase with LL-37 in one of three active groups or placebo, and 4 weeks of follow-up.
Events reported
The authors report no safety concerns regarding local or systemic adverse events, and describe the material as well tolerated over the four weeks it was used.

Dolkar et al., 2018, PMID 29665030

Events reported
A single-person report from a phase 1 melanoma study of LL-37 in cutaneous metastases. A 63-year-old woman with stage IIIC melanoma, who had already progressed on nivolumab and on combination chemotherapy, received the study peptide. About 45 days after starting, she presented with multiple verrucous papules and a vesiculo-bullous lesion on the trunk and extremities; 11 of 12 skin biopsies showed a lichenoid inflammatory infiltrate with eosinophils and an overlying atypical squamous epithelial proliferation with keratoacanthoma-like features, and 11 of 12 showed no spongiosis. All lesions resolved within 2 months of stopping. Because two prior regimens had been given, the report does not establish this peptide as the sole cause.

Trial events do not establish a complete safety profile.

Published research

Grouped by the kind of study. Select one to narrow what is shown below.

Laboratory (in vitro)(4)

Laboratory (in vitro)

NMR structure of the cathelicidin-derived human antimicrobial peptide LL-37 in dodecylphosphocholine micelles.

Porcelli F, Verardi R, Shi L, Henzler-Wildman KA, Ramamoorthy A, Veglia G., Biochemistry, 2008;47(20):5565-5572

published

  • Determined the three-dimensional structure of LL-37 in dodecylphosphocholine micelles by NMR, the peptide having been incorporated into the micelles for the measurement. Under those conditions the peptide adopts a helix-break-helix conformation with both termini unstructured and solvent-exposed; the N-terminal helical region is the more dynamic and the C-terminal helix the more structured and solvent-protected. The break between the helices sits at K12 and is described as probably stabilised by a hydrophobic cluster of I13, F17 and I20 together with a salt bridge between K12 and E16. The peptide is adsorbed on the micelle surface, its hydrophilic face toward the water and its hydrophobic face buried in the micelle.
View publication →
Laboratory (in vitro)

Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3.

Sørensen OE, Follin P, Johnsen AH, Calafat J, Tjabringa GS, Hiemstra PS, Borregaard N., Blood, 2001;97(12):3951-3959

published

  • Reports that the precursor hCAP-18 showed no detectable cleavage inside cells after phagocytosis, but was cleaved to LL-37 in exocytosed material, and that of the three known serine proteases of azurophil granules, proteinase 3 was solely responsible for that cleavage. The authors describe this as the first detailed account of how this human peptide is generated from its precursor protein.
View publication →
Laboratory (in vitro)

Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity.

Oren Z, Lerman JC, Gudmundsson GH, Agerberth B, Shai Y., Biochemical Journal, 1999;341 (Pt 3):501-513

published

  • Reports that LL-37 exists in an equilibrium between monomers and oligomers in solution at very low concentrations, and is significantly resistant to breakdown by proteases both in solution and when bound to zwitterionic membranes (modelling mammalian cells) and to negatively charged membranes (modelling bacterial cells). Comparison with an N-terminally truncated form assigned the N-terminus a role in that resistance and in the peptide's haemolytic activity, but not in its antimicrobial activity.
  • Reports that in vitro the peptide is cytotoxic to bacterial and to ordinary eukaryotic cells alike. Polarised attenuated total reflectance Fourier-transform infrared spectroscopy found it predominantly α-helical and oriented nearly parallel to the surface of zwitterionic membranes, which the authors state does not support a channel-forming model but rather a detergent-like, carpet-type interaction.
Context

The membrane work describes an interaction, not a receptor. It also describes it as non-selective: the same surface-lying helix that disrupts bacterial membranes acts on ordinary mammalian membranes, and the authors measured haemolytic activity alongside antibacterial activity. Selectivity is the open question in this structural literature, not a settled property.

View publication →
Laboratory (in vitro)

The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes.

Gudmundsson GH, Agerberth B, Odeberg J, Bergman T, Olsson B, Salcedo R., European Journal of Biochemistry, 1996;238(2):325-332

published

  • Reports the complete human gene, FALL39: 1,963 base pairs in four exons, with exons 1 to 3 coding a signal sequence and the cathelin region and exon 4 the mature peptide. The authors state their results indicate FALL39 is the only member of the cathelin gene family in the human genome. Antibody staining located the peptide in granulocytes, and the mature peptide isolated from those cells after degranulation was determined by structural analysis to be LL-37.
  • To obtain material for antibacterial assays, the synthetic precursor peptide was digested with dipeptidyl-peptidase I; the authors report that the mature LL-37 produced this way is a potent antibacterial peptide. No organism-by-organism figures are given in the abstract.
View publication →

Human study (phase not stated)(1)

Human study (phase not stated)n = 34

Grönberg et al., 2014 (title withheld on this site; see the publication record)

Grönberg A, Mahlapuu M, Ståhle M, Whately-Smith C, Rollman O., Wound Repair and Regeneration, 2014;22(5):613-621

published

A first-in-man, randomised, double-blind, placebo-controlled study of the synthetic human peptide, in 34 participants with hard-to-heal venous leg ulcers. It comprised a 3-week open-label run-in period on placebo, a 4-week randomised double-blind phase with LL-37 in one of three active groups or placebo, and 4 weeks of follow-up.

  • The healing rate constant in the lowest-concentration group was approximately sixfold higher than in the placebo group (p = 0.003). The abstract does not give the number of participants in each group.
  • The healing rate constant in the middle-concentration group was approximately threefold higher than in the placebo group, a difference that was not statistically significant (p = 0.088).
  • In an analysis of square-root-transformed wound-area data, the lowest- and middle-concentration groups each differed from their own pretreatment values (p < 0.001 and p = 0.011 respectively), which the authors report as healing. This is a within-group comparison against each group's starting values, not a comparison with placebo.
  • Mean ulcer area decreased by 68% in the lowest-concentration group and by 50% in the middle-concentration group. The abstract gives no p-value and no placebo-group figure for this measure.
  • No difference in healing was observed between the group given the highest concentration and placebo.
  • The authors report no safety concerns regarding local or systemic adverse events, and describe the material as well tolerated over the four weeks it was used.
Limitations

The human record verified for this page is two publications: one randomised study of 34 participants, in people with leg ulcers, over four weeks — the lowest of three concentrations separated from placebo on healing rate constant (p = 0.003), the middle one's difference did not reach statistical significance (p = 0.088), and the highest did not separate from placebo — and one report of skin findings in a single person who had also had two other regimens. Neither is a general finding about this peptide, and neither was conducted with research material.

View publication →

Human phase 1(1)

Human phase 1n = 1

Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: A detailed examination of the clinicopathologic features.

Dolkar T, Trinidad CM, Nelson KC, Amaria RN, Nagarajan P, Torres-Cabala CA, Ivan D, Prieto VG, Tetzlaff MT, Curry JL, Aung PP., Journal of Cutaneous Pathology, 2018;45(7):539-544

published

  • A single-person report from a phase 1 melanoma study of LL-37 in cutaneous metastases. A 63-year-old woman with stage IIIC melanoma, who had already progressed on nivolumab and on combination chemotherapy, received the study peptide. About 45 days after starting, she presented with multiple verrucous papules and a vesiculo-bullous lesion on the trunk and extremities; 11 of 12 skin biopsies showed a lichenoid inflammatory infiltrate with eosinophils and an overlying atypical squamous epithelial proliferation with keratoacanthoma-like features, and 11 of 12 showed no spongiosis. All lesions resolved within 2 months of stopping. Because two prior regimens had been given, the report does not establish this peptide as the sole cause.
Limitations

The human record verified for this page is two publications: one randomised study of 34 participants, in people with leg ulcers, over four weeks — the lowest of three concentrations separated from placebo on healing rate constant (p = 0.003), the middle one's difference did not reach statistical significance (p = 0.088), and the highest did not separate from placebo — and one report of skin findings in a single person who had also had two other regimens. Neither is a general finding about this peptide, and neither was conducted with research material.

View publication →

References

Published studies reviewed (6)

  1. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. — Gudmundsson GH, Agerberth B, Odeberg J, Bergman T, Olsson B, Salcedo R., European Journal of Biochemistry, 1996;238(2):325-332
    DOI 10.1111/j.1432-1033.1996.0325z.x · PMID 8681941
  2. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. — Sørensen OE, Follin P, Johnsen AH, Calafat J, Tjabringa GS, Hiemstra PS, Borregaard N., Blood, 2001;97(12):3951-3959
    DOI 10.1182/blood.v97.12.3951 · PMID 11389039
  3. Structure and organization of the human antimicrobial peptide LL-37 in phospholipid membranes: relevance to the molecular basis for its non-cell-selective activity. — Oren Z, Lerman JC, Gudmundsson GH, Agerberth B, Shai Y., Biochemical Journal, 1999;341 (Pt 3):501-513
    PMID 10417311 · PMC1220385
  4. NMR structure of the cathelicidin-derived human antimicrobial peptide LL-37 in dodecylphosphocholine micelles. — Porcelli F, Verardi R, Shi L, Henzler-Wildman KA, Ramamoorthy A, Veglia G., Biochemistry, 2008;47(20):5565-5572
    DOI 10.1021/bi702036s · PMID 18439024 · PMC5873590
  5. Grönberg et al., 2014 (title withheld on this site; see the publication record) — Grönberg A, Mahlapuu M, Ståhle M, Whately-Smith C, Rollman O., Wound Repair and Regeneration, 2014;22(5):613-621
    DOI 10.1111/wrr.12211 · PMID 25041740
  6. Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: A detailed examination of the clinicopathologic features. — Dolkar T, Trinidad CM, Nelson KC, Amaria RN, Nagarajan P, Torres-Cabala CA, Ivan D, Prieto VG, Tetzlaff MT, Curry JL, Aung PP., Journal of Cutaneous Pathology, 2018;45(7):539-544
    DOI 10.1111/cup.13262 · PMID 29665030

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