期刊
PROTEIN ENGINEERING DESIGN & SELECTION
卷 23, 期 6, 页码 431-440出版社
OXFORD UNIV PRESS
DOI: 10.1093/protein/gzq013
关键词
cancer; cell-internalized ligands; enzyme prodrug therapy; phage display; beta-lactamase
资金
- National Institute of Health [RO1CA112091]
- SD Ireland Cancer Research Fund
- NATIONAL CANCER INSTITUTE [R01CA112091] Funding Source: NIH RePORTER
The present study was focused on identifying cancer cell-specific internalizing ligands using a new kind of phage display library in which the linear or cysteine-constrained random peptides were at amino-terminus fusion to catalytically active P99 beta-lactamase molecules. The size and quality of libraries were comparable to other reported phage display systems. Several cancer cell-specific binding and internalizing beta-lactamase-peptide fusion ligands were isolated by selecting these libraries on the live BT-474 human breast cancer cells. The identified ligands shared several significant motifs, which showed their selectivity and possible binding to some common cancer cell targets. The beta-lactamase fusion made the whole process of clone screening efficient and simple. The ligands selected from such libraries do not require peptide synthesis and modifications, and can be used directly for applications that require ligand tracking. In addition, the selected beta-lactamase-peptide ligands have a potential for their direct use in targeted enzyme prodrug therapy. The cancer-specific peptides can also be adopted for other kinds of targeted delivery protocols requiring cell-specific affinity reagents. This is first report on the selection of cell-internalized enzyme conjugates using phage display technology, which opens the possibility for new fusion libraries with other relevant enzymes.
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