Description

Technical Parameters

Introduction

peptides

product-1400-1400

Products Description

### Systematic review of LL37 peptide

LL37 is the only antimicrobial peptide (AMP) in the human body that belongs to the **cathelicidin family**. It is composed of **37 amino acids** and its name comes from the first two leucine residues (Leucine-Leucine). As an important component of the innate immune system, LL37 not only plays a key role in antimicrobial defense, but also has multiple biological functions such as immunoregulation and promoting tissue repair. This article will systematically explain **structural characteristics, physicochemical properties, biological functions, application fields, color characteristics, advantages and limitations** and **future research directions**.

### 1. Structural characteristics

#### 1. Primary structure

The amino acid sequence of LL37 is:

`LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES`

Its N-terminus is rich in hydrophobic amino acids (such as leucine and phenylalanine), while its C-terminus is mainly composed of positively charged arginine (Arg) and lysine (Lys), forming an **amphiphilic structure**, which is the basis for its interaction with microbial membranes.

#### 2. Secondary structure

- **α-helical conformation**: In a hydrophobic environment (such as a cell membrane) or a low ionic strength solution, LL37 forms an **α-helix** by folding, which promotes its insertion into the microbial lipid bilayer.

- **β-folding or random coil**: In a high salt concentration or polar environment, LL37 may exist in a disordered conformation with reduced activity.

#### 3. Three-dimensional structure

Through nuclear magnetic resonance (NMR) analysis, the three-dimensional structure of LL37 in a simulated membrane environment is shown as a **bent helical structure**, with clear divisions between the hydrophobic and hydrophilic surfaces, which is conducive to targeting negatively charged pathogen membranes.

### 2. Physical and chemical properties

#### 1. Basic parameters

- **Molecular weight**: about **4.5 kDa** (exact value: 4493.4 Da).

- **Isoelectric point (pI)**: about **10.5-11.0** (due to the presence of 6 arginine and 5 lysine residues).

- **Solubility**: easily soluble in water or physiological buffer (such as PBS), but may precipitate in high salt solutions due to charge shielding effects.

#### 2. Stability

- **Temperature sensitivity**: stable at 4°C, high temperature (>60°C) easily leads to denaturation and inactivation.

- **Protease sensitivity**: easily degraded by trypsin and pepsin, chemical modification (such as D-amino acid substitution) or nanocarrier encapsulation is required to improve stability.

#### 3. Color characteristics

- **Pure state**: lyophilized powder is **white or off-white**, solution state is **colorless and transparent**.

- **Complex color development**: it may appear light yellow after combining with certain metal ions (such as zinc and copper), but there is no significant functional effect.

### 3. Biological function

#### 1. Antibacterial activity

- **Broad-spectrum antibacterial**: effective against Gram-positive bacteria (such as Staphylococcus aureus), Gram-negative bacteria (such as Escherichia coli), fungi (such as Candida albicans) and enveloped viruses (such as HSV, influenza virus).

- **Mechanism of action**: destroy the integrity of microbial membranes through electrostatic adsorption, resulting in leakage of contents; neutralize endotoxins (such as LPS) at the same time.

#### 2. Immunomodulation

- **Chemotaxis**: Recruit neutrophils and monocytes to the site of infection.

- **Regulate inflammatory response**: Inhibit excessive inflammation (such as regulating the NF-κB pathway) and promote the balance between pro-inflammatory factors (IL-6, TNF-α) and anti-inflammatory factors (IL-10).

#### 3. Tissue repair and regeneration

- **Promote angiogenesis**: Stimulate endothelial cell migration by activating EGFR and MAPK pathways.

- **Wound healing**: Upregulate collagen synthesis and accelerate epithelialization (clinical trials show that it can shorten the healing time of diabetic ulcers by 30%).

#### 4. Anticancer activity

- **Selective killing**: Target cancer cell membranes (due to the externalization of phosphatidylserine in cancer cell membranes) and induce apoptosis (such as breast cancer cell line MDA-MB-231).

- **Inhibit metastasis**: Block MMP-9 expression and reduce tumor invasion (lung metastasis is reduced by 50% in animal models).

### 4. Application fields

#### 1. Anti-infection treatment

- **Local infection**: Wound dressings for drug-resistant bacteria (such as hydrogels containing LL37).

- **Systemic infection**: Combined with antibiotics, it can reduce the MIC value by 4-8 times.

#### 2. Dermatology

- **Psoriasis**: Regulate Th17 cell response and reduce erythema and scaling (65% effective rate in Phase II clinical trial).

- **Atopic dermatitis**: Repair skin barrier function and reduce Staphylococcus aureus colonization.

#### 3. Tumor treatment

- **Adjuvant chemotherapy**: Enhance the killing of cisplatin against ovarian cancer cells (synergy index 0.7).

- **Targeted delivery**: Combined with magnetic nanoparticles to achieve local high-concentration release in tumors.

#### 4. Biomaterials

- **Implant coating**: Prevent orthopedic implant-related infections (infection rate reduced by 90% in animal models).

- **Tissue engineering scaffold**: Promotes stem cell differentiation into vascular endothelial cells.

### 5. Advantages and limitations

#### 1. Advantages

- **Broad-spectrum and low drug resistance**: Multi-target mechanism reduces the risk of drug resistance.

- **Multifunctionality**: Has antibacterial, immunomodulatory and repair-promoting functions.

- **Biocompatibility**: Naturally expressed in the human body, with low side effects.

#### 2. Limitations

- **Poor stability**: Half-life in the body is only 1-2 hours, requiring frequent dosing.

- **Potential toxicity**: May cause hemolysis at high concentrations (HC50 is about 100 μM).

- **High production cost**: The cost of chemically synthesized LL37 with a purity of >95% is about US$500/g.

### 6. Future research directions

1. **Structural optimization**: Develop analogs (such as 17BIPHE2) to enhance stability and targeting.

2. **Delivery system**: liposomes, exosomes or microneedle patches for sustained release and local administration.

3. **Combination therapy**: Combined with immune checkpoint inhibitors (such as PD-1 antibodies) to enhance anti-cancer effects.

4. **Clinical transformation**: Promote Phase III clinical trials for sepsis and COVID-19 (by inhibiting viral entry).

### Summary

LL37 peptide, as a key molecule connecting innate immunity and tissue repair, has shown great potential in the treatment of infectious diseases, chronic wounds and cancer. Despite the challenges of stability and toxicity, its clinical application prospects are broad with the advancement of nanotechnology and gene editing. Future research needs to further clarify its molecular mechanism and promote multidisciplinary cross-innovation to achieve the goal of precision medicine.