LL-37

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.

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.