Peptide name : Multivalent DR5 binding peptides, TRAILmim/DR5 (2m)

Source/Organism : Not found

Linear/Cyclic : Linear

Chirality : L

Peptide length: 16

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Kd (Binding constants of TRAIL mimics): 664 ± 18 nMol/L

Cell line : HCT 116

Cancer type : Colon cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 1975.3021 Dalton

Aliphatic index : 0.912

Instability index : 39.0938

Hydrophobicity (GRAVY) : -0.712

Isoelectric point : 8.9552

Charge (pH 7) : 1.7415

Aromaticity : 0.062

Molar extinction coefficient (cysteine, cystine): (5500, 5625)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : -0.032

Missing amino acid : H,T,P,M,E,F,S,Y,A

Most occurring amino acid : R

Most occurring amino acid frequency : 3

Least occurring amino acid : W

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.1, 0.2, 0.3)

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

1 : Pavet V, et al. Multivalent DR5 peptides activate the TRAIL death pathway and exert tumoricidal activity. Cancer Res. 2010; 70:1101-10. doi: 10.1158/0008-5472.CAN-09-2889

Paper title : Multivalent DR5 peptides activate the TRAIL death pathway and exert tumoricidal activity.

Doi : https://doi.org/10.1158/0008-5472.CAN-09-2889

Abstract : Ongoing clinical trials are exploring anticancer approaches based on signaling by TRAIL, a ligand for the cell death receptors DR4 and DR5. In this study, we report on the selective apoptotic effects of multivalent DR5 binding peptides (TRAIL(mim/DR5)) on cancer cells in vitro and in vivo. Surface plasmon resonance revealed up to several thousand-fold increased affinities of TRAIL(mim/DR5)-receptor complexes on generation of divalent and trivalent molecules, the latter of which was achieved with a conformationally restricted adamantane core. Notably, only multivalent molecules triggered a substantial DR5-dependent apoptotic response in vitro. In tumor models derived from human embryonic kidney cells or primary foreskin fibroblasts, TRAIL(mim/DR5) peptides exerted a cancer cell-selective action that could synergize with resveratrol in a manner independent of p53. In a xenograft model of human colon cancer, a divalent TRAIL(mim/DR5) peptide inhibited tumor growth. Our results offer a proof-of-principle for the development of synthetic small molecules to trigger the TRAIL apoptosis pathway for cancer therapy.