Peptide name : K4F6K4

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 14

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : CCK-8 assay

Assay time : 48-h

Activity : IC50 = 62.64 ± 9.55 μg/mL

Cell line : A-549

Cancer type : Lung Cancer

Other activity : Antimicrobial

Amino acid composition bar chart :

Molecular mass : 1926.4365 Dalton

Aliphatic index : 0

Instability index : -1.45

Hydrophobicity (GRAVY) : -1.028

Isoelectric point : 10.845

Charge (pH 7) : 7.7521

Aromaticity : 42.85

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

Hydrophobic/hydrophilic ratio : 0.75

hydrophobic moment : -0.142

Missing amino acid : A,C,D,E,G,H,I,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 : F

Least occurring amino acid frequency : 6

Secondary structure fraction (Helix, Turn, Sheet): (57., 0, 42.)

SMILES Notation: NCCCC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(=O)O

1 : Yang D, et al. Therapeutic Effects of Synthetic Triblock Amphiphilic Short Antimicrobial Peptides on Human Lung Adenocarcinoma. Pharmaceutics. 2022; 14:(unknown pages). doi: 10.3390/pharmaceutics14050929

Paper title : Therapeutic Effects of Synthetic Triblock Amphiphilic Short Antimicrobial Peptides on Human Lung Adenocarcinoma.

Doi : https://doi.org/10.3390/pharmaceutics14050929

Abstract : Because of their unique properties, antimicrobial peptides (AMPs) represent a potential reservoir of novel anticancer therapeutic agents. However, only a few AMPs can kill tumors with high efficiency, and obtaining inexpensive anticancer AMPs with strong activity is still a challenge. In our previous work, a series of original short amphiphilic triblock AMP (K_nF_mK_n) analogues were developed which were demonstrated to exert excellent effects on bacterial infection, both in vitro and in vivo. Herein, the overall objectives were to assess the potent tumoricidal capacities of these analogues against human lung cancer cell line A549 and the underlying mechanism. The results of the CCK-8 assay revealed that the precise modification of the peptides' primary sequences could modulate their tumoricidal potency. In the tumoricidal progress, positive charge and hydrophobicity were the key driving forces. Among these peptides, K₄F₆K₄ displayed the most remarkable tumoricidal activity. Furthermore, the excellent anticancer capacity of K₄F₆K₄ was proven by the live/dead cell staining, colony formation assay, and tumor growth observations on xenografted mice, which indicated that K₄F₆K₄ might be a promising drug candidate for lung cancer, with no significant adverse effects in vitro or in vivo. In addition, the cell apoptosis assay using flow cytometry, the morphology observations using the optical microscope, confocal microscopy using CellMask™ Deep Red staining, and scanning electron microscope suggested that membrane disruption was the primary mechanism of its antitumor action. Through analyzing the structure-activity relationship, it was found that the amount of positive charge required for K_nF_mK_n to exert its optimal tumoricidal effect was more than that needed for the antimicrobial activity, while the optimal proportion of hydrophobicity was less. Our findings suggest that further analysis of the structure-activity relationship of AMPs' primary sequence variations will be beneficial. Hopefully, this work can provide guiding principles in designing peptide-based therapeutics for lung cancer.