Selection of trkB-binding peptides from a phage-displayed random peptide library

作     者：马仲才 吴晓兰 曹明媚 潘卫 朱分禄 陈景山 戚中田 

作者机构：Department of MicrobiologySecond Military Medical University Department of PsychologyYale University School of Medicine 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2003年第46卷第1期

页      面：77-86页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 

基　　金：the National Natural Science Foundation of China (Grant Nos. 39825116 & 30070168). References 

主　　题：phage display, random peptide library, brain-derived neurotrophic factor, trkB antagonist. 

摘      要：Brain-derived neurotrophic factor (BDNF) shows potential in the treatment of neurode-generative diseases, but the therapeutic application of BDNF has been greatly limited because it is too large in molecular size to permeate blood-brain barrier. To develop low-molecular-weight BDNF-like peptides, we selected a phage-displayed random peptide library using trkB expressed on NIH 3T3 cells as target in the study. With the strategy of peptide library incubation with NIH 3T3 cells and competitive elution with 1 mg/mL of BDNF in the last round of selection, the specific phages able to bind to the natural conformation of trkB and antagonize BDNF binding to trkB were enriched effectively. Five trkB-binding peptides were obtained, in which a core sequence of CRA/TXfXXfXXC (X represents the random amino acids, f represents T, L or I) was identified. The BDNF-like activity of these five peptides displayed on phages was not observed, though all of them antagonized the activity of BDNF in a dose-dependent manner. Similar results were obtained with the synthetic peptide of C1 clone, indicating that the 5 phage-derived peptides were trkB antagonists. These low-molecular-weight antagonists of trkB may be of potential application in the treatment of neuroblastoma and chronic pain. Meanwhile, the obtained core sequence also could be used as the base to construct the secondary phage-displayed peptide library for further devel-opment of small peptides mimicking BDNF activity.