Peptide name : DR-5 binding peptide

Source/Organism : Not found

Linear/Cyclic : Linear

Chirality : L

Peptide length: 11

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Not found

Cell line : COLO-205

Cancer type : Not found

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 1398.6949 Dalton

Aliphatic index : 0.972

Instability index : 18.8818

Hydrophobicity (GRAVY) : 0.2364

Isoelectric point : 8.8597

Charge (pH 7) : 1.8245

Aromaticity : 0.181

Molar extinction coefficient (cysteine, cystine): (2980, 3105)

Hydrophobic/hydrophilic ratio : 0.83333333

hydrophobic moment : -0.145

Missing amino acid : W,Q,P,M,E,F,S,D,N,A,G

Most occurring amino acid : Y

Most occurring amino acid frequency : 2

Least occurring amino acid : K

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.1, 0, 0.5)

SMILES Notation: CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O

1 : Vrielink J, et al. Synthetic constrained peptide selectively binds and antagonizes death receptor 5. FEBS J. 2010; 277:1653-65. doi: 10.1111/j.1742-4658.2010.07590.x

Paper title : Synthetic constrained peptide selectively binds and antagonizes death receptor 5.

Doi : https://doi.org/10.1111/j.1742-4658.2010.07590.x

Abstract : Apoptosis or programmed cell death is an inherent part of the development and homeostasis of multicellular organisms. Dysregulation of apoptosis is implicated in the pathogenesis of diseases such as cancer, neurodegenerative diseases and autoimmune disorders. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to induce apoptosis by binding death receptor (DR)4 (TRAIL-R1) and DR5 (TRAIL-R2), which makes TRAIL an interesting and promising therapeutic target. To identify peptides that specifically interact with DR5, a disulfide-constrained phage display peptide library was screened for binders towards this receptor. Phage-displayed peptides were identified that bind specifically to DR5 and not to DR4, nor any of the decoy receptors. We show that the synthesized peptide, YCKVILTHRCY, in both monomeric and dimeric forms, binds specifically to DR5 in such a way that TRAIL binding to DR5 is inhibited. Surface plasmon resonance studies showed higher affinity towards DR5 for the dimeric form then the monomeric form of the peptide, with apparent K(d) values of 40 nm versus 272 nm, respectively. Binding studied on cell lines by flow cytometry analyses showed concentration-dependent binding. Upon co-incubation with increasing concentrations of TRAIL, the peptide binding was reduced. Moreover, both the monomeric and dimeric forms of the peptide reduced TRAIL-induced cell death in Colo205 colon carcinoma cells. The peptide, YCKVILTHRCY, or its derivates, may be a useful investigative tool for dissecting signalling via DR5 relative to DR4 or could act as a lead peptide for the development of therapeutic agents in diseases with dysregulated TRAIL-signalling.