Cancer cell-specific internalizing ligands from phage displayed beta-lactamase-peptide fusion libraries.
Cancer cell-specific internalizing ligands from phage displayed beta-lactamase-peptide fusion libraries.
复制标题
来自噬菌体的癌细胞特异性内化配体展示了β-内酰胺酶-肽融合文库。
DOI：
10.1093/protein/gzq013
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Krag,DavidN
中科院分区：
文献类型：
--
作者：
Shukla,GirjaS;Krag,DavidN
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 β-lactamase molecules. The size and quality of libraries were comparable to other reported phage display systems. Several cancer cell-specific binding and internalizing β-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 β-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 β-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.
