Peptide name : D-LAK-120-A

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : D

Peptide length: 25

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 72-h

Activity : IC50 between 4.0 and 5.5 μM

Cell line : HCC-827

Cancer type : Lung Adenocarcinoma

Other activity : Antimicrobial

Amino acid composition bar chart :

Molecular mass : 2703.4876 Dalton

Aliphatic index : 0

Instability index : 7.744

Hydrophobicity (GRAVY) : 0.508

Isoelectric point : 10.845

Charge (pH 7) : 7.7521

Aromaticity : 4

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : infinite

hydrophobic moment : 0

Missing amino acid : A,C,D,E,F,G,H,I,K,L,M,N,P,Q,R,S,T,V,W,Y

Most occurring amino acid : k

Most occurring amino acid frequency : 8

Least occurring amino acid : w

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (96, 0, 36)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)O

1 : Patil SM and Kunda NK. Anticancer activity of D-LAK-120A, an antimicrobial peptide, in non-small cell lung cancer (NSCLC). Biochimie. 2022; 201:7-17. doi: 10.1016/j.biochi.2022.06.011

Paper title : Anticancer activity of D-LAK-120A, an antimicrobial peptide, in non-small cell lung cancer (NSCLC).

Doi : https://doi.org/10.1016/j.biochi.2022.06.011

Abstract : Non-small cell lung cancer (NSCLC) is a major cause of global cancer mortalities and accounts for approximately 80-85% of reported lung cancer cases. Conventional chemotherapeutics show limited application because of poor tumor selectivity and acquired drug resistance. Antimicrobial peptides (AMPs) have gained much attention as potential anticancer therapeutics owing to their high potency and high target selectivity and specificity with limited scope for drug resistance. In this study, D-LAK (D-LAK-120A), a cationic AMP, was evaluated for its anticancer efficacy in various NSCLC cell lines. D-LAK peptide demonstrated enhanced cytotoxicity in A549, H358, H1975, and HCC827 cell lines with inhibitory concentrations between 4.0 and 5.5 μM. An increase in the lactate dehydrogenase (LDH) levels and propidium iodide (PI) uptake across compromised membrane suggested membranolytic activity as an inhibition pathway. In addition, we found D-LAK induced lung cancer cell apoptosis and arrested cells in the S phase (DNA synthesis) of cell cycle. Moreover, a decreased mitochondrial membrane potential and elevated ROS levels were observed after D-LAK treatment, suggesting induction of mitochondria-mediated apoptosis. Additionally, D-LAK inhibited single cell proliferation and cancer cell migration in vitro. The tumor reduction observed in the 3D spheroid assay further suggests the potential use of D-LAK as an anticancer agent for NSCLC treatment. Our results postulate innovative insights on the anticancer mechanism of D-LAK, which may contribute to its further development into preclinical studies and a potential therapeutic.