Peptide name : FRAP-4

Source/Organism : Not found

Linear/Cyclic : Linear

Chirality : L

Peptide length: 4

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : IC50 : 7 µM

Cell line : NOS4

Cancer type : Ovarian cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 620.653 Dalton

Aliphatic index : 0

Instability index : -67.65

Hydrophobicity (GRAVY) : -1.5

Isoelectric point : 4.05

Charge (pH 7) : -1.2371

Aromaticity : 0.5

Molar extinction coefficient (cysteine, cystine): (11000, 11000)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : 0.0509

Missing amino acid : P,I,M,K,F,D,N,G,C,R,H,Q,S,Y,L,A,V

Most occurring amino acid : W

Most occurring amino acid frequency : 2

Least occurring amino acid : E

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.2, 0, 0.7)

SMILES Notation: C[C@@H](O)[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(=O)O

1 : Yoshimori A, et al. Structure-based design of an agonistic peptide targeting Fas. Apoptosis. 2005; 10:323-9. doi: 10.1007/s10495-005-0806-6

Paper title : Structure-based design of an agonistic peptide targeting Fas.

Doi : https://doi.org/10.1007/s10495-005-0806-6

Abstract : A small agonistic peptide FRAP-4 (WEWT, Fas reactive peptide-4) that binds to the human Fas molecule was discovered using our computer screening strategy named the Amino acid Complement Wave (ACW) method, which is based on the complementarities of interacting amino acids between comprehensive testing peptides and a target protein surface pocket. In silico docking studies demonstrated the specific interaction of FRAP-4 with the main Fas ligand (FasL) binding domain in the Fas molecule. An octamer of this peptide produced by carboxyl terminal linkages of polylysine branches (MAP), (FRAP-4)8-MAP, effectively induced apoptosis in human ovarian cancer cell line NOS4 cells that was associated with the activation of caspases-8, -9 and -3, and the cleavage of PARP. Alanine substitution of the N-terminal W in FRAP-4 resulted in complete loss of FasL-mimetic action of (FRAP-4)8-MAP, suggesting that the aromatic functionality at the N-terminal position W appears to play an essentially important role in Fas binding ability. These observations indicate that the FasL-mimetic peptide should serve as an excellent starting point for the design of effective compounds with FasL-mimetic activity. Furthermore, the ACW method for the structure-based design of optimized small peptides against receptor molecules such as Fas could open new avenues for the development of peptide mimetic and nonpeptidic organic forms to generate novel effective pharmaceuticals.