LL-37 5mg

What is LL-37 ?

LL-37 is a 37-residue cathelicidin-derived antimicrobial peptide (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), the only human member of the cathelicidin family. Research has examined its broad-spectrum antimicrobial activity, its role in wound healing and angiogenesis, and its immunomodulatory effects on epithelial tissues.

LL-37 is the C-terminal peptide of hCAP-18, the human cathelicidin precursor. After neutrophils release hCAP-18, the enzyme proteinase 3 cuts LL-37 free (Sorensen et al., Blood, 2001). It was first predicted as FALL-39 from a human bone-marrow cDNA library (Agerberth et al., Proc Natl Acad Sci USA, 1995). Gudmundsson and colleagues (Eur J Biochem, 1996) then isolated the mature peptide from human granulocytes. The name records its two N-terminal leucines and its 37 residues, and its international nonproprietary name is ropocamptide.

Eleven basic and five acidic residues give a net charge of +6 at neutral pH. The sequence has no cysteine, methionine or tryptophan, so there are no disulfides and no oxidation-prone residues. In lipid micelles it forms a curved amphipathic helix-bend-helix across residues 2 to 31, with a disordered C-terminal tail (Wang, J Biol Chem, 2008). Each LL-37 5mg vial holds white lyophilised powder.

LL-37 Research Applications

• Antimicrobial : Turner and colleagues (Antimicrob Agents Chemother, 1998) reported MICs below 10 µg/ml, even in 100 mM NaCl. Targets included Pseudomonas aeruginosa (mucoid and resistant strains too), Escherichia coli, Staphylococcus aureus and vancomycin-resistant enterococci.
• Salt sensitivity : in the same study MRSA, Proteus mirabilis and Candida albicans resisted LL-37 in 100 mM NaCl but were susceptible in low-salt media.
• Angiogenesis : Koczulla and colleagues (J Clin Invest, 2003) reported endothelial proliferation and vessel-like structures, acting through formyl peptide receptor-like 1 (FPRL1).
• Wound models : Carretero and colleagues (J Invest Dermatol, 2008) reported keratinocyte migration in vitro and faster wound closure in ob/ob mice after adenoviral gene transfer.
• Immune signalling : in psoriasis, LL-37 binds self-DNA, and the complexes activate plasmacytoid dendritic cells through Toll-like receptor 9 (Lande et al., Nature, 2007).

Work has since extended to biofilm and antiviral assays, and to wound closure in airway epithelial cells (Shaykhiev et al., Am J Physiol Lung Cell Mol Physiol, 2005). Most findings are in vitro or preclinical. Human data are limited. In the first-in-man trial of topical LL-37 in 34 people with hard-to-heal venous leg ulcers, the highest concentration showed no difference from placebo (Grönberg et al., Wound Repair Regen, 2014).

LL-37 vs KR-12

KR-12 is the smallest fragment of LL-37 that keeps antimicrobial activity. It spans residues 18 to 29, Lys-Arg-Ile-Val-Gln-Arg-Ile-Lys-Asp-Phe-Leu-Arg (KRIVQRIKDFLR). Wang (J Biol Chem, 2008) solved both structures in lipid micelles, and the pair is now used to map which parts of the full sequence matter. The full-length peptide carries the whole set of reported activities: antimicrobial, angiogenic and immunomodulatory. It also aggregates in solution, and serum weakens its antimicrobial activity (Dürr et al., Biochim Biophys Acta, 2006). KR-12 is easier to keep in solution and cleaner for structure-activity work, but its findings do not automatically transfer. LL-37 is the choice when the endogenous human molecule is the point of the study.

Research Overview

LL-37 is a 37-residue, cationic, amphipathic antimicrobial peptide corresponding to the C-terminal region of the human cathelicidin precursor hCAP-18, with the 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 formula C₂₀₅H₃₄₀N₆₀O₅₃, molecular weight 4493.3 g/mol and CAS number 154947-66-7. It is the only human member of the cathelicidin family of antimicrobial peptides, carrying a net charge of +6 with no cysteine, methionine or tryptophan in its sequence. The peptide was first predicted as FALL-39 from a human bone-marrow cDNA library (Agerberth et al., Proc Natl Acad Sci USA, 1995), the mature peptide was isolated from human granulocytes and its gene characterised by Gudmundsson and colleagues (Eur J Biochem, 1996), and its release from the inactive precursor hCAP-18 by the neutrophil enzyme proteinase 3 was characterised by Sorensen and colleagues (Blood, 2001). In membrane-mimetic environments LL-37 folds into an amphipathic alpha-helix, the conformation solved alongside that of its smallest antimicrobial fragment KR-12 in lipid micelles by Wang (J Biol Chem, 2008), and the field is reviewed comprehensively by Dürr and colleagues (Biochim Biophys Acta, 2006).

Research has examined LL-37's broad-spectrum antimicrobial activity, its role in wound healing and angiogenesis, and its immunomodulatory effects on epithelial tissues. The foundational antimicrobial study is Turner and colleagues (Antimicrob Agents Chemother, 1998), who reported activity against Pseudomonas aeruginosa, including mucoid and antibiotic-resistant strains, Escherichia coli, Staphylococcus aureus and vancomycin-resistant enterococci, with later work extending to anti-biofilm and antiviral assays. Angiogenesis and wound-healing work includes the report of endothelial proliferation and new vessel formation in model systems by Koczulla and colleagues (J Clin Invest, 2003), keratinocyte migration and improved wound healing in diabetic mice by Carretero and colleagues (J Invest Dermatol, 2008), and stimulated proliferation and wound closure in airway epithelial cells by Shaykhiev and colleagues (Am J Physiol Lung Cell Mol Physiol, 2005). Epithelial immunomodulation work includes chemotactic and cytokine-modulating activities and, in psoriasis, the formation of complexes with self-DNA that activate plasmacytoid dendritic cells through Toll-like receptor 9 (Lande et al., Nature, 2007).

It is worth being direct about the state of the human evidence, because the in-vitro literature is large and the human literature is not. Most findings come from cell-culture assays and animal models, and the human clinical record is limited to a single randomised, placebo-controlled trial of topical LL-37 in hard-to-heal venous leg ulcers (Grönberg et al., Wound Repair Regen, 2014), which reported that treatment was safe and well tolerated, that the highest concentration tested showed no difference from placebo, and that effects on healing-related predictors at the two lower concentrations warranted further investigation. LL-37 holds no marketing authorisation in any jurisdiction and is supplied here as lyophilised powder, supplier-tested, with the certificate published on this page and independent third-party verification pending, strictly for in-vitro laboratory research use only.

Storage and Reconstitution

Move vials to the freezer on arrival and keep them dark and dry. In solution the risks are aggregation and adsorption to plastic, not oxidation. Keep solutions cold, limit dilution steps in plastic tubes, and freeze single-use aliquots for longer storage.

Vials are sold on their own, without bacteriostatic water for mixing or other supplies.

How to reconstitute and handle

• LL-37 is a cationic peptide that adsorbs to plastic surfaces and aggregates in solution; work with cold diluents, minimise dilution steps in plastic vessels and prepare fresh working dilutions rather than storing them.
• Handle under aseptic laboratory conditions using sterile equipment throughout reconstitution and aliquoting, and avoid repeated freeze-thaw cycles. Prepare measured single-use aliquots from reconstituted stock.

For the full method, see the peptide reconstitution guide and the reconstitution calculator.

Research References

• LL-37, the only human member of the cathelicidin family of antimicrobial peptides (Dürr et al., Biochim Biophys Acta, 2006)
• An angiogenic role for the human peptide antibiotic LL-37/hCAP-18 (Koczulla et al., J Clin Invest, 2003)

Published research on LL-37 is indexed on PubMed. See our full UK buyer's guide for LL-37.