Peptide name : RP-7

Source/Organism : Migration and invasion enhancer 1 (MIEN1)

Linear/Cyclic : Linear

Chirality : L

Peptide length: 7

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 24-h

Activity : IC50 = 110.12 ± 4.23 µM

Cell line : MCF-7

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 797.0205 Dalton

Aliphatic index : 1.528

Instability index : 69.5714

Hydrophobicity (GRAVY) : 1.0429

Isoelectric point : 8.2497

Charge (pH 7) : 0.7502

Aromaticity : 0

Molar extinction coefficient (cysteine, cystine): (1, 0)

Hydrophobic/hydrophilic ratio : 6

hydrophobic moment : -0.514

Missing amino acid : A,D,E,F,G,H,K,M,N,Q,S,T,W,Y

Most occurring amino acid : P

Most occurring amino acid frequency : 2

Least occurring amino acid : R

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (14., 28., 42.)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCNC(=N)N)C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)O

1 : Tripathi AK, et al. Short peptides based on the conserved regions of MIEN1 protein exhibit anticancer activity by targeting the MIEN1 signaling pathway. J Biol Chem. 2024; 300:105680. doi: 10.1016/j.jbc.2024.105680

Paper title : Short peptides based on the conserved regions of MIEN1 protein exhibit anticancer activity by targeting the MIEN1 signaling pathway.

Doi : https://doi.org/10.1016/j.jbc.2024.105680

Abstract : Migration and invasion enhancer 1 (MIEN1) overexpression characterizes several cancers and facilitates cancer cell migration and invasion. Leveraging conserved immunoreceptor tyrosine-based activation motif and prenylation motifs within MIEN1, we identified potent anticancer peptides. Among them, bioactive peptides LA3IK and RP-7 induced pronounced transcriptomic and protein expression changes at sub-IC50 concentrations. The peptides effectively inhibited genes and proteins driving cancer cell migration, invasion, and epithelial-mesenchymal transition pathways, concurrently suppressing epidermal growth factor-induced nuclear factor kappa B nuclear translocation in metastatic breast cancer cells. Specifically, peptides targeted the same signal transduction pathway initiated by MIEN1. Molecular docking and CD spectra indicated the formation of MIEN1-peptide complexes. The third-positioned isoleucine in LA3IK and CVIL motif in RP-7 were crucial for inhibiting breast cancer cell migration. This is evident from the limited migration inhibition observed when MDA-MB-231 cells were treated with scrambled peptides LA3IK SCR and RP-7 SCR. Additionally, LA3IK and RP-7 effectively suppressed tumor growth in an orthotopic breast cancer model. Notably, mice tolerated high intraperitoneal (ip) peptide doses of 90 mg/Kg well, surpassing significantly lower doses of 5 mg/Kg intravenously (iv) and 30 mg/Kg intraperitoneally (ip) used in both in vivo pharmacokinetic studies and orthotopic mouse model assays. D-isomers of LA3IK and RP-7 showed enhanced anticancer activity compared to their L-isomers. D-LA3IK remained stable in mouse plasma for 24 h with 75% remaining, exhibiting superior pharmacokinetic properties over D/L-RP-7. In summary, our findings mark the first report of short peptides based on MIEN1 protein sequence capable of inhibiting cancer signaling pathways, effectively impeding cancer progression both in vitro and in vivo.