Peptide name : LK-LE3

Source/Organism : Synthetic

Linear/Cyclic : Cyclic

Chirality : L

Peptide length: 30

C-terminal modification: Cyclic

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 24-h

Activity : IC50 = 10.2 µM at pH 6

Cell line : HeLa

Cancer type : Cervical Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 3642.5545 Dalton

Aliphatic index : 1.82

Instability index : 21.6

Hydrophobicity (GRAVY) : 0.2667

Isoelectric point : 8.761

Charge (pH 7) : 2.0942

Aromaticity : 0

Molar extinction coefficient (cysteine, cystine): (2, 1)

Hydrophobic/hydrophilic ratio : 1.1429

hydrophobic moment : -0.137

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

Most occurring amino acid : L

Most occurring amino acid frequency : 14

Least occurring amino acid : C

Least occurring amino acid frequency : 2

Secondary structure fraction (Helix, Turn, Sheet): (80, 0, 46.)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CS)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)O

1 : Chang L, et al. One New Acid-Activated Hybrid Anticancer Peptide by Coupling with a Desirable pH-Sensitive Anionic Partner Peptide. ACS Omega. 2023; 8:7536-7545. doi: 10.1021/acsomega.2c06766

Paper title : One New Acid-Activated Hybrid Anticancer Peptide by Coupling with a Desirable pH-Sensitive Anionic Partner Peptide.

Doi : https://doi.org/10.1021/acsomega.2c06766

Abstract : Anticancer peptides (ACPs) are promising antitumor resources, and developing acid-activated ACPs as more effective and selective antitumor drugs would represent new progress in cancer therapy. In this study, we designed a new class of acid-activated hybrid peptides LK-LE by altering the charge shielding position of the anionic binding partner LE based on the cationic ACP LK and investigated their pH response, cytotoxic activity, and serum stability, in hoping to achieve a desirable acid-activatable ACP. As expected, the obtained hybrid peptides could be activated and exhibit a remarkable antitumor activity by rapid membrane disruption at acidic pH, whereas its killing activity could be alleviated at normal pH, showing a significant pH response compared with LK. Importantly, this study found that the peptide LK-LE3 with the charge shielding in the N-terminal of LK displayed notably low cytotoxicity and more stability, demonstrating that the position of charge masking is extremely important for the improvement of peptide toxicity and stability. In short, our work opens a new avenue to design promising acid-activated ACPs as potential targeting agents for cancer treatment.