Identification of C10 biotinylated camptothecin (CPT-10-B) binding peptides using T7 phage display screen on a QCM device
- 作者：Yoichi Takakusagi ; Kaori Takakusagi ; Kouji Kuramochi ; Susumu Kobayashi ; Fumio Sugawara ; Kengo Sakaguchi
- 关键词：Camptothecin ; T7 phage display ; QCM ; Peptide
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 December 2007
- 卷：15
- 期：24
- 页码：7590-7598
- 文件大小：1089 K
摘要
A peptide sequence that can bind to camptothecin (CPT), a natural cytotoxic compound, was screened for using a T7 phage display system combined with a cuvette type quartz crystal microbalance (QCM) device. In this screen, after only 10 min of monitoring of the interaction between injected T7 phage pool with immobilized C10 biotinylated CPT (CPT-10-B) on a gold electrode surface, six different kinds of phage (A–F) were identified as judged by the size of PCR product on agarose gel electrophoresis. Injection of each single phage (A–E) pool individually caused a frequency decrease, suggesting interaction with the immobilized CPT-10-B. In addition, the peptide sequence displayed on phages A–C is consistent with chemical and biological studies of the interaction of CPTs with topoisomerase I (TopI), human E prostanoid receptor third cytoplasmic polypeptide, and a series of esterases. The efficacy of T7 phage display screening for small molecules on QCM devices, target discovery from primary peptide sequence, and application of this strategy to various drug-like small molecules are discussed.