Peptide name : MEL-dKLA

Source/Organism : Venom base

Linear/Cyclic : Linear

Chirality : Mix

Peptide length: 45

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : MTS assay

Assay time : 24h

Activity : IC50 : 0.85 μM

Cell line : RAW264.7

Cancer type : Lung cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 4668.7054 Dalton

Aliphatic index : 1.215

Instability index : 30.7467

Hydrophobicity (GRAVY) : 0.0822

Isoelectric point : 12

Charge (pH 7) : 10.7511

Aromaticity : 0.022

Molar extinction coefficient (cysteine, cystine): (5500, 5500)

Hydrophobic/hydrophilic ratio : 1.64705882

hydrophobic moment : 0.5765

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

Most occurring amino acid : K

Most occurring amino acid frequency : 9

Least occurring amino acid : P

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.5, 0.2, 0.3)

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](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)N1CCC[C@H]1C(=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)NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)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](CC(C)C)C(=O)N[C@@H](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)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C

1 : Lee C, et al. Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide. J Immunother Cancer. 2019; 7:147. doi: 10.1186/s40425-019-0610-4

Paper title : Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide.

Doi : https://doi.org/10.1186/s40425-019-0610-4

Abstract : BACKGROUND: Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating immune cells. Macrophages are broadly categorized as M1 or M2 types, and TAMs have been shown to express an M2-like phenotype. TAMs promote tumor progression and contribute to resistance to chemotherapies. Therefore, M2-like TAMs are potential targets for the cancer immunotherapy. In this study, we targeted M2-like TAMs using a hybrid peptide, MEL-dKLA, composed of melittin (MEL), which binds preferentially to M2-like TAMs, and the pro-apoptotic peptide d (KLAKLAK)₂ (dKLA), which induces mitochondrial death after cell membrane penetration. METHODS: The M1 or M2-differentiated RAW264.7 cells were used for mitochondrial colocalization and apoptosis test in vitro. For in vivo study, the murine Lewis lung carcinoma cells were inoculated subcutaneously in the right flank of mouse. The dKLA, MEL and MEL-dKLA peptides were intraperitoneally injected at 175 nmol/kg every 3 days. Flow cytometry analysis of tumor-associated macrophages and immunofluorescence staining were performed to investigate the immunotherapeutic effects of MEL-dKLA. RESULTS: We showed that MEL-dKLA induced selective cell death of M2 macrophages in vitro, whereas MEL did not disrupt the mitochondrial membrane. We also showed that MEL-dKLA selectively targeted M2-like TAMs without affecting other leukocytes, such as T cells and dendritic cells, in vivo. These features resulted in lower tumor growth rates, tumor weights, and angiogenesis in vivo. Importantly, although both MEL and MEL-dKLA reduced numbers of CD206+ M2-like TAMs in tumors, only MEL-dKLA induced apoptosis in CD206+ M2-like TAMs, and MEL did not induce cell death. CONCLUSION: Taken together, our study demonstrated that MEL-dKLA could be used to target M2-like TAMs as a promising cancer therapeutic agent.