Cathelicidin LL 37 (human)
[CAS# 154947-66-7]

Identification

• Classification: Biochemical >> Peptide
• Name: Cathelicidin LL 37 (human)
• Synonyms: Cathelicidin LL 37 (human); Cathelicidin LL-37; LL 37; Peptide LL 37 (human gene FALL39 antibacterial); Protein CAP 18 (rabbit cationic antimicrobial 37-amino acid fragment); hCAP 18; (4S)-5-[[(2S)-6-amino-1-[[(2S,3S)-1-[[2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-5-carbamimidamido-1-[[(2S,3R)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-hydroxyethyl]amino]-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid
• Protein Sequence: LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES
• Molecular Formula: C₂₀₅H₃₄₀N₆₀O₅₃
• Molecular Weight: 4493.27
• CAS Registry Number: 154947-66-7
• SMILES: CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)N

Discovory and Applicatios

Cathelicidin LL‑37 is a human antimicrobial peptide that plays a central role in the innate immune response. It is derived from the C‑terminal region of the precursor protein known as human cationic antimicrobial protein of 18 kDa (hCAP18), which is encoded by the CAMP gene. LL‑37 is a linear 37‑amino‑acid peptide with a net positive charge and an amphipathic helical structure that enables it to interact with and disrupt microbial membranes. It is expressed in a variety of cell types including neutrophils, epithelial cells of the skin, respiratory tract, and gastrointestinal system, and other immune cells, and is released in response to infection or injury as part of the first line of defense against pathogens.

The discovery of LL‑37 emerged from studies on mammalian antimicrobial peptides during the 1990s, when researchers identified a family of peptides called cathelicidins that exhibited broad‑spectrum antimicrobial activity. In humans, only one cathelicidin has been identified: hCAP18, which is proteolytically cleaved to release LL‑37 at sites of infection or inflammation. Unlike many conventional antibiotics that target specific cellular processes, LL‑37 kills microorganisms through its physical interaction with microbial membranes, leading to membrane disruption and cell death. This mechanism relies on the peptide’s amphipathic α‑helical structure that allows it to bind negatively charged bacterial membranes preferentially, destabilize lipid bilayers, and form pores or lesions in pathogen membranes.

In addition to direct antimicrobial activity, LL‑37 exerts immunomodulatory effects that contribute to host defense. It can chemoattract immune cells such as neutrophils, monocytes, and T cells to sites of infection, modulate cytokine production, and influence the maturation and activation of antigen‑presenting cells. LL‑37 also interacts with host receptors such as formyl peptide receptor‑like 1 (FPRL1) to affect immune cell recruitment and function. These immunomodulatory properties enhance both innate and adaptive immune responses, helping to contain infection while shaping subsequent immune reactions.

LL‑37 has also been studied for its anti‑biofilm activities against bacterial communities that form protective matrices, which are often resistant to traditional antibiotics. In laboratory models of biofilm formation, LL‑37 inhibits initial bacterial adhesion, disrupts established biofilms, and enhances the susceptibility of bacteria to other antimicrobial agents. These properties have spurred interest in developing LL‑37 and its derivatives as potential therapeutic agents for treating chronic wound infections, device‑associated biofilms, and antibiotic‑resistant pathogens. However, although the peptide shows promise in vitro and in preclinical models, there are challenges to clinical application, including susceptibility to proteolytic degradation in physiological environments, potential toxicity at high concentrations, and high production costs.

Beyond its antimicrobial and immunomodulatory functions, LL‑37 participates in wound healing and tissue repair. It can promote re‑epithelialization, angiogenesis, and cellular proliferation in damaged tissues, supporting restoration of barrier integrity following injury. These wound healing effects are partly mediated through interactions with host cell signaling pathways and growth factors, highlighting the multifaceted roles of LL‑37 beyond simple microbial killing. Research has also examined LL‑37 in the context of inflammatory diseases, autoimmune conditions, and cancer, with evidence that dysregulated LL‑37 expression may contribute to pathophysiology in certain contexts.

Although LL‑37 itself has not yet achieved regulatory approval as a therapeutic antimicrobial agent, it remains a model compound for host defense peptides and a subject of extensive research. Strategies to enhance its clinical potential include developing more stable analogues, optimizing delivery methods, and combining it with existing treatments to overcome limitations such as proteolytic degradation and toxicity. The breadth of research on LL‑37 underscores its significance as a natural antimicrobial, immune modulator, and potential template for novel peptide‑based therapeutics.

References

Porcelli F, Verardi R, Shi L, Henzler‑Wildman KA, Ramamoorthy A, Veglia G (2008) NMR structure of the cathelicidin‑derived human antimicrobial peptide LL‑37 in dodecylphosphocholine micelles. Biochemistry 47(20) 5565–5572 DOI: 10.1021/bi702036s

Ridyard KE, Overhage J (2021) The potential of human peptide LL‑37 as an antimicrobial and anti‑biofilm agent. Antibiotics 10(6) 650 DOI: 10.3390/antibiotics10060650

Human antimicrobial/host defense peptide LL‑37 may prevent the spread of a local infection through multiple mechanisms: an update (2025) Inflammation Research 74 article 36 DOI: 10.1007/s00011-025-02005-8