Peptide name : MEL-Pep

Source/Organism : Synthetic analog of Melittin

Linear/Cyclic : Linear

Chirality : L

Peptide length: 26

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : CCK-8 assay

Assay time : 24-h

Activity : IC50 = 4.36 μM

Cell line : BEL-7402/5-FU

Cancer type : Liver Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 2907.5455 Dalton

Aliphatic index : 1.238

Instability index : 26.65

Hydrophobicity (GRAVY) : -0.126

Isoelectric point : 12

Charge (pH 7) : 6.7551

Aromaticity : 3.846

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

Hydrophobic/hydrophilic ratio : 1.1667

hydrophobic moment : -0.058

Missing amino acid : C,D,E,F,H,M,N,P,Y

Most occurring amino acid : K

Most occurring amino acid frequency : 5

Least occurring amino acid : V

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (42., 15., 42.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)CN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C

1 : Ke M, et al. MEL-pep, an analog of melittin, disrupts cell membranes and reverses 5-fluorouracil resistance in human hepatocellular carcinoma cells. Int J Biochem Cell Biol. 2018; 101:39-48. doi: 10.1016/j.biocel.2018.05.013

Paper title : MEL-pep, an analog of melittin, disrupts cell membranes and reverses 5-fluorouracil resistance in human hepatocellular carcinoma cells.

Doi : https://doi.org/10.1016/j.biocel.2018.05.013

Abstract : Chemotherapy resistance represents a major obstacle in the treatment of patients with hepatocellular carcinoma (HCC). The purpose of this study was to investigate the anti-cancer effect of MEL-pep, a novel analog of the natural antibacterial peptide melittin (MEL), on human 5-fluorouracil-resistant HCC cells (BEL-7402/5-FU) and to clarify the molecular mechanisms involved in these effects. We found that MEL-pep inhibited the proliferation of BEL-7402/5-FU cells and reversed 5-FU resistance in vitro. MEL-pep directly bound to BEL-7402/5-FU cells and disrupted the cell membrane. P-glycoprotein (P-gp) plays an important role in the development of resistance to anticancer drugs. We found that MEL-pep inhibited P-gp expression and increased the intracellular accumulation of the P-gp substrate rhodamine-123 in BEL-7402/5-FU cells. Additionally, the phosphorylation of Akt and NF-κB/p65 nuclear translocation was all inhibited by MEL-pep. Insulin - like growth factor I, a phosphatidylinositol 3 kinase(PI3K) /protein kinase B(AKT) agonist, reversed MEL-pep induced P-gp suppression. Therefore, MEL-pep inhibited P-gp expression by deactivating the PI3K/Akt signaling pathway. Finally, in a BEL-7402/5-FU cell-derived xenograft tumor model in mice, we found that the intratumoral administration of MEL-pep inhibited tumor growth in a dose-dependent manner. Thus, MEL-pep could be a promising candidate in the treatment of chemotherapy resistant HCC.