Peptide name : RA-3

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : Mix

Peptide length: 20

C-terminal modification: Linear

N-terminal modification : Amidation

Non-natural peptide information:

Assay type : MTT assay

Assay time : 48-h

Activity : IC50 = 28.4 μM

Cell line : MDA-MB-231

Cancer type : Breast Cancer

Other activity : Anticancer

Amino acid composition bar chart :

Molecular mass : 2207.5323 Dalton

Aliphatic index : 0.83

Instability index : 65.885

Hydrophobicity (GRAVY) : -0.14

Isoelectric point : 9.9862

Charge (pH 7) : 1.762

Aromaticity : 15

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

Hydrophobic/hydrophilic ratio : 2.1667

hydrophobic moment : -0.280

Missing amino acid : C,H,M,N,P,Q,T,V,Y

Most occurring amino acid : G

Most occurring amino acid frequency : 5

Least occurring amino acid : R

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (25, 35, 35)

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

1 : Han Z, et al. A frog-derived bionic peptide with discriminative inhibition of tumors based on integrin αvβ3 identification. Biomater Sci. 2020; 8:5920-5930. doi: 10.1039/d0bm01187h

Paper title : A frog-derived bionic peptide with discriminative inhibition of tumors based on integrin αvβ3 identification.

Doi : https://doi.org/10.1039/d0bm01187h

Abstract : Aureins, natural active peptides extracted from skin secretions of Australian bell frogs, have become a research focus due to the antitumor effects caused by lysing cell membranes. However, clinical translation of Aureins is still limited by non-selective toxicity between normal and cancer cells. Herein, by structure-activity relationship analysis and rational linker design, a dual-function fusion peptide RA3 is designed by tactically fusing Aurein peptide A1 with strong anticancer activity, with a tri-peptide with integrin αvβ3-binding ability which was screened in our previous work. Rational design and selection of fusion linkers ensures α-helical conformation and active functions of this novel fusion peptide, inducing effective membrane rupture and selective apoptosis of cancer cells. The integrin binding and tumor recognition ability of the fusion peptide is further validated by fluorescence imaging in cell and mouse models, in comparison with the non-selective A1 peptide. Meanwhile, increased stability and superior therapeutic efficacy are achieved in vivo for the RA3 fusion peptide. Our study highlights that aided by computational simulation technologies, the biomimetic fusion RA3 peptide has been successfully designed, surmounting the poor tumor-selectivity of the natural defensive peptide, serving as a promising therapeutic agent for cancer treatment.