Peptide name : LL-37 Analogue 4

Source/Organism : Synthetic Analog of LL-37

Linear/Cyclic : Linear

Chirality : L

Peptide length: Not available

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 48-h

Activity : IC50 = 3.9 µg/mL

Cell line : A-549

Cancer type : Lung Cancer

Other activity : Antimicrobial and Anticancer

Amino Acid Composition Bar Chart : Not available

Molecular mass : Not available

Aliphatic index : Not available

Instability index : Not available

Hydrophobicity (GRAVY) : Not available

Isoelectric point : Not available

Charge (pH 7) : Not available

Aromaticity : Not available

Molar extinction coefficient (cysteine, cystine): Not available

Hydrophobic/hydrophilic ratio : Not available

hydrophobic moment : Not available

Missing amino acid : Not available

Most occurring amino acid : Not available

Most occurring amino acid frequency : Not available

Least occurring amino acid : Not available

Least occurring amino acid frequency : Not available

3D-structure: Not available

Secondary structure fraction (Helix, Turn, Sheet): Not available

SMILES Notation: Not available

Molecular descriptors: Not available

ADMET properties: Not available

1 : Tzitzilis A, et al. Cationic amphipathic peptide analogs of cathelicidin LL-37 as a probe in the development of antimicrobial/anticancer agents. J Pept Sci. 2020; 26:e3254. doi: 10.1002/psc.3254

Paper title : Cationic amphipathic peptide analogs of cathelicidin LL-37 as a probe in the development of antimicrobial/anticancer agents.

Doi : https://doi.org/10.1002/psc.3254

Abstract : Cathelicidin LL-37 belongs to the class of human defense peptides and is overexpressed in many cancers. Segments of LL-37 derived through biochemical processes have a wide range of activities. In this study, novel analogs of the 13-amino acid cathelicidin 17-29 amide segment F17 KRIV21 QR23 IK25 DF27 LR-NH₂ were prepared and examined for their antimicrobial and hemolytic activities, as well as for their cytotoxicity on cancer bronchial epithelial cells. Selected substitutions were performed on residues R23 and K25 in the hydrophilic side, V21 and F27 in the hydrophobic side of the interphase, and F17 that interacts with cell membranes. Specific motifs IIKK and LLKKL with anticancer and antimicrobial activities isolated from animals were also inserted into the 17-29 fragment to investigate how they affect activity. Substitution of the amino-terminal positive charge by acetylation and replacement of lysine by the aliphatic leucine in the peptide analog Ac-FKRIVQRIL25 DFLR-NH₂ resulted in significant cytotoxicity against A549 cancer cells with an IC₅₀ value 3.90 μg/mL, with no cytotoxicity to human erythrocytes. The peptide Ac-FKRIVQI23 IKK26 FLR-NH₂ , which incorporates the IIKK motif and the peptides FKRIVQL23 L24 KK26 L27 LR-NH₂ and Ac-FKRIVQL23 L24 KK26 L27 LR-NH₂ , which incorporate the LLKKL motif, displayed potent antimicrobial activity against gram-negative bacteria (MIC 3-7.5 μg/mL) and substantial cytotoxicity against bronchial epithelial cancer cells, (IC₅₀ 12.9-9.8 μg/mL), with no cytotoxic activity for human erythrocytes. The helical conformation of the synthetic peptides was confirmed by circular dichroism. Our study shows that appropriate substitutions, mainly in positions of the interphase, as well as the insertion of the motifs IIKK and LLKKL in the cathelicidin 17-29 segment, may lead to the preparation of effective biological compounds.