LL-37, scrambled

Product Name: LL-37, scrambled

Sequence One Letter Code: GLKLRFEFSKIKGEFLKTPEVRFRDIKLKDNRISVQR

Sequence Three Letter Code: Gly-Leu-Lys-Leu-Arg-Phe-Glu-Phe-Ser-Lys-Ile-Lys-Gly-Glu-Phe-Leu-Lys-Thr-Pro-Glu-Val-Arg-Phe-Arg-Asp-Ile-Lys-Leu-Lys-Asp-Asn-Arg-Ile-Ser-Val-Gln-Arg

Chemical Formula:C205H340N60O53

Molecular Weight: 4493.6

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Inflammation and Immunology Research

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: LL-37, scrambled is a synthetic control peptide containing the same amino acid composition as native LL-37 arranged in a randomized sequence. The altered sequence disrupts the amphipathic α-helical structure responsible for LL-37’s antimicrobial and immunomodulatory activities. This peptide is used as a negative control to distinguish sequence-specific biological effects from nonspecific charge- or length-dependent interactions. It supports mechanistic studies in innate immunity, membrane biology, and antimicrobial peptide research.

Current Research: LL-37 is the only human cathelicidin-derived antimicrobial peptide and plays a multifaceted role in innate immunity. Beyond its broad-spectrum antimicrobial activity, LL-37 modulates inflammatory signaling, chemotaxis, angiogenesis, and wound healing. Structurally, LL-37 adopts an amphipathic α-helical conformation under membrane-mimetic conditions, a feature that underlies its ability to interact with microbial membranes and host receptors. LL-37, scrambled is a synthetic control peptide that preserves the exact amino acid composition of native LL-37 but arranges the residues in a randomized sequence. This alteration disrupts the ordered amphipathic structure required for biological activity, making it a critical negative control in mechanistic studies. The functional properties of LL-37 are highly sequence-dependent. Its antimicrobial activity relies on a spatial arrangement of cationic and hydrophobic residues that form a helical amphipathic surface. This topology enables electrostatic attraction to negatively charged bacterial membranes, followed by membrane insertion and destabilization. Scrambling the sequence redistributes these residues, preventing formation of the same helical amphipathic architecture. Although the scrambled peptide retains overall charge and length, its inability to adopt the native structure significantly reduces or abolishes membrane-disruptive capacity. In antimicrobial assays, LL-37, scrambled is used to distinguish specific membrane-targeting effects from nonspecific interactions related to peptide charge density. Native LL-37 demonstrates bactericidal activity against Gram-positive and Gram-negative organisms, whereas the scrambled control typically exhibits minimal antimicrobial potency under comparable conditions. This comparison confirms that bacterial killing depends on defined sequence motifs rather than generic cationic properties. The scrambled peptide is equally important in immunomodulatory research. LL-37 engages host receptors such as formyl peptide receptor 2 (FPR2/ALX), modulates Toll-like receptor (TLR) signaling, and enhances cellular uptake of nucleic acids. These interactions contribute to cytokine production, dendritic cell activation, and inflammatory responses. Using the scrambled control allows researchers to confirm that receptor activation or signaling modulation is driven by specific structural determinants of LL-37 rather than by generalized membrane perturbation or electrostatic binding. Membrane biology studies frequently employ LL-37, scrambled to evaluate structure–function relationships. Biophysical analyses such as circular dichroism spectroscopy demonstrate that native LL-37 forms α-helical structures in lipid environments, whereas the scrambled variant typically shows reduced helical propensity. Liposome leakage assays further reveal diminished membrane-permeabilizing effects for the scrambled peptide. These comparisons provide direct evidence linking amphipathic helix formation to biological activity. In studies of host–pathogen interactions, the scrambled peptide controls for potential artifacts arising from peptide concentration or physicochemical characteristics. For example, when assessing binding to lipopolysaccharide (LPS) or bacterial surface components, inclusion of LL-37, scrambled ensures that observed effects are sequence-specific. Similarly, in cell culture experiments evaluating cytotoxicity or chemotactic responses, the scrambled control helps determine whether outcomes reflect targeted receptor engagement or nonspecific peptide exposure. The peptide also supports investigations into intracellular signaling and immune modulation. LL-37 influences pathways involving NF-κB activation, inflammasome assembly, and cytokine expression. By comparing responses to native and scrambled peptides, researchers can delineate which signaling events require preserved sequence orientation and structural integrity. This distinction is particularly important in translational research exploring LL-37-derived therapeutics. Beyond innate immunity, LL-37 has been implicated in autoimmune diseases, cancer biology, and tissue regeneration. In these contexts, scrambled controls validate conclusions regarding sequence-dependent interactions with cell surface receptors, extracellular matrix components, or growth factors. In summary, LL-37, scrambled is a synthetic control peptide that maintains the amino acid composition of native LL-37 while disrupting its amphipathic α-helical structure. By lacking the structural features responsible for antimicrobial and immunomodulatory activity, it serves as a rigorous negative control. Its application strengthens mechanistic studies in innate immunity, membrane biophysics, and antimicrobial peptide research by enabling clear differentiation between sequence-specific biological effects and nonspecific physicochemical interactions.