Peptide Research

In-depth research profiles with mechanisms of action, key findings, and peer-reviewed citations from PubMed.

LL-37 (Cathelicidin)

LL-37 | Cathelicidin | CAP18 | hCAP18

Molecular Weight4493.33 g/mol
CAS Number154947-66-7
SequenceLeu-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
Antimicrobial Peptides Innate Immunity Wound Healing Anti-Biofilm Immunomodulation

Mechanism of Action

LL-37 is the only human cathelicidin antimicrobial peptide, derived from the C-terminal cleavage of the 18-kDa precursor protein hCAP18 by proteinase 3. It is a 37-amino-acid amphipathic alpha-helical peptide produced by neutrophils, macrophages, epithelial cells, and other cell types as part of the innate immune defense.

LL-37's antimicrobial mechanism involves direct membrane disruption of microbial cells. Its amphipathic structure — with a hydrophobic face and a cationic (positively charged) face — enables it to insert into negatively charged microbial membranes, causing pore formation and cell lysis. It is active against a broad spectrum of Gram-positive and Gram-negative bacteria, fungi, and enveloped viruses. Crucially, LL-37 also disrupts bacterial biofilms at sub-bactericidal concentrations, a property that distinguishes it from many conventional antibiotics.

Beyond direct antimicrobial activity, LL-37 serves as a potent immunomodulator. It recruits immune cells to infection sites by acting as a chemoattractant for neutrophils, monocytes, and T-cells via the formyl peptide receptor-like 1 (FPRL1). It promotes wound healing by stimulating angiogenesis and re-epithelialization. LL-37 also modulates Toll-like receptor signaling, enhancing the immune response to bacterial products while dampening potentially harmful excessive inflammatory responses.

Key Research Findings

  • Hancock & Sahl (2006) reviewed antimicrobial peptides including LL-37 as key effectors of innate immunity with direct microbicidal and immunomodulatory functions.
  • Overhage et al. (2008) demonstrated LL-37 inhibits Pseudomonas aeruginosa biofilm formation at 0.5 mcg/mL — well below its bactericidal concentration — through interference with quorum sensing.
  • Heilborn et al. (2003) showed LL-37 is upregulated during wound healing and promotes re-epithelialization of human skin wounds.
  • Vandamme et al. (2012) reviewed LL-37's dual role as antimicrobial agent and wound healing promoter.

References

  1. PMID: 17159151
  2. PMID: 18391006
  3. PMID: 12558053
  4. PMID: 22387025

Dosage in Research

In vitro antimicrobial studies use 1-32 mcg/mL. Anti-biofilm activity observed at 0.5-4 mcg/mL. Wound healing studies in animals use topical application of 10-100 mcg/wound.

Storage & Handling

Store lyophilized powder at -20C. LL-37 is susceptible to proteolytic degradation; reconstitute in sterile water and store at 2-8C for short-term use. Avoid repeated freeze-thaw cycles.

Frequently Asked Questions

What is LL-37?

LL-37 is the only human cathelicidin antimicrobial peptide — a 37-amino-acid peptide that serves as a key component of innate immune defense. It has direct antimicrobial, anti-biofilm, and wound healing properties.

How does LL-37 fight biofilms?

LL-37 disrupts bacterial biofilm formation at concentrations below its bactericidal threshold. This is significant because biofilms are a major cause of antibiotic-resistant chronic infections. The mechanism involves interference with bacterial quorum sensing and surface attachment.

Is LL-37 only antimicrobial?

No. Beyond direct microbial killing, LL-37 modulates immune cell recruitment, promotes wound healing via angiogenesis and re-epithelialization, and regulates inflammatory responses through Toll-like receptor signaling modulation.

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