Peptide name : R-C16

Source/Organism : R-Lycosin-I

Linear/Cyclic : Linear

Chirality : L

Peptide length: 23

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : CCK-8 assay

Assay time : 24-h

Activity : IC50 ~ 5 µM

Cell line : A-549

Cancer type : Lung Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 2928.4287 Dalton

Aliphatic index : 0.808

Instability index : 32.1609

Hydrophobicity (GRAVY) : -0.621

Isoelectric point : 12

Charge (pH 7) : 4.8528

Aromaticity : 13.04

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

Hydrophobic/hydrophilic ratio : 1.0909

hydrophobic moment : -0.574

Missing amino acid : C,D,K,N,P,Q,T,V,Y

Most occurring amino acid : R

Most occurring amino acid frequency : 7

Least occurring amino acid : G

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (34., 8.6, 30.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@@H](N)CCCNC(=N)N)[C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CC(C)C)C(=O)O

1 : Jian C, et al. The Roles of Fatty-Acid Modification in the Activity of the Anticancer Peptide R-Lycosin-I. Mol Pharm. 2018; 15:4612-4620. doi: 10.1021/acs.molpharmaceut.8b00605

Paper title : The Roles of Fatty-Acid Modification in the Activity of the Anticancer Peptide R-Lycosin-I.

Doi : https://doi.org/10.1021/acs.molpharmaceut.8b00605

Abstract : We previously reported that R-lycosin-I, modified by amino acid substitution from lycosin-I, was a peptide with anticancer activity and a linear amphipathic α-helix conformation and that it can induce cancer cell apoptosis and inhibit cell proliferation. However, the anticancer activity of R-lycosin-I was not highly improved. In order to further improve the anticancer activity of R-lycosin-I, fatty acids with different chain lengths from 12 to 20 carbons were introduced to the N-terminal of R-lycosin-I to yield five lipopeptides (R-C₁₂, R-C₁₄, R-C₁₆, R-C₁₈, R-C₂₀). The physicochemical properties of the five lipopeptides were determined by hydrodynamic size, ζ-potential, and circular dichroism spectroscopy, respectively. Then, the cytotoxic activity of these lipopeptides in A549 cells was evaluated with serum-containing and serum-free media, respectively, showing their anticancer activities were all increased through fatty-acid modification. This may be a result of the increased hydrophobicity and the enhanced interaction with the cancer cell membrane. The cytotoxic activity of R-C₁₆ was 3-4-fold higher than that of the original R-lycosin-I and also was the strongest among all five lipopeptides, whether in serum or serum-free conditions. Compared with R-lycosin-I, the lactate dehydrogenase (LDH) leakage assay and scanning electron microscopy (SEM) indicated that R-C₁₆ had a weakly destructive effect on the cancer cell membrane, but it might cause apoptosis to exert an anticancer activity. Finally, the impacts of fatty-acid length on the physicochemical properties and the anticancer potential of peptide were discussed. Our data consolidate work on fatty-acid-modified anticancer peptides.