Synthesis of DR5-derived complementary peptide FR-11 and its inhibitory effect on TRAIL-mediated cell apoptosis
10.3724/SP.J.1008.2008.00892
- Author:
Yun GAO
1
Author Information
1. Department of Molecular Biology and Biochemistry
- Publication Type:Journal Article
- Keywords:
Antisense peptide;
Apoptosis;
DR5;
TRAIL
- From:
Academic Journal of Second Military Medical University
2010;29(8):892-895
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To synthesize DR5-derived complementary peptide(s) that can influence the function of TRAIL and to observe its(their) inhibitory effect on TRAIL-mediated cell death. Methods: A software was designed to identify the matching domains of two known peptide sequences according to the theory of Proteomic Code. The antisense homology box sequences between DR5 and its ligand TRAIL were searched by the designed software. Possibly active peptide(s) was/were selected and synthesized based on the structural information of TRAIL-DR5 complex. The binding between TRAIL molecule and the selected peptide(s) was examined by ELISA; the inhibitory effect of the selected peptide(s) against TRAIL-induced cell death was studied by cellular experiments. Results: Ten complementary peptide sequences were obtained based on software selection and structural analyzing. One active DR5-derived peptide FR-11 was selected with ligand-binding analysis using ELISA; FR-11 showed specific binding to TRAIL in a dose-dependant manner and blocked the binding of TRAIL with DR5. The matching rate between FR-11 and TRAIL 97-103aa was higher than 50%. Computer analysis showed that FR-11 corresponded to the extracellular domain of DRS, a key binding site to TRAIL. Further study indicated that FR-11 inhibited TRAIL-induced apoptosis of SW1990 cells and L929 cells in a dose-dependant manner; the inhibitory effect of FR-11 was more potent when the concentration of TRAIL was low, suggesting that it inhibited the binding between TRAIL and death receptor. Conclusion: The software designed based on the theory of Proteomic Code can be used to select complementary peptides which influence the interaction between ligand and receptor. The selected peptide FR-11 can bind to the ligand TRAIL and subsequently inhibit the biological function of the ligand.
