一种特异性识别非小细胞肺癌A549细胞的小分子肽

A Novel Specific Small Molecule Peptide for Non-small Cell Lung Cancer Cell A549

应用"一个珠子一个化合物"的组合化学肽库,以期筛选得到特异性识别非小细胞肺癌细胞(A549)的小分子肽.初次筛选共得到29个与A549阳性结合的珠子,经氨基酸序列分析后发现含有-NGXG-肽链结构的序列共有10个.选择cNGQGEQc作进一步的细胞特异性研究,发现cNGQGEQc与非小细胞肺癌A549、Calu-1及H178的粘附特异性明显高于其他细胞系,对cNGQGEQc的结构分析显示,-NGXG-及六肽长度对小分子肽与A549细胞的粘附非常重要.标记FITC的小分子肽cNGQGEQc能与A549细胞发生特异性结合.用抗整合素的抗体(!1～6,"v和#1～5)阻断小分子肽与A549细胞表面的相应受体结合,结果显示,α3与$亚单位的任何组合均对cNGQGEQc与A549细胞的粘附有明显的阻断作用.结果表明,小分子肽cNGQGEQc是通过细胞表面整合素α3与非小细胞肺癌A549发生特异性结合.

To screen small molecule peptide specific binding to non-small cell lung cancer cell （A549） using the ＂ one-bead one-peptide＂ combinatorial library. Twenty-nine positive beads binding to A549 cell were totally obtained after primary screening. Consensus peptide sequence of-NGXG- was identified by amino acid sequencing in ten beads. Peptide cNGQGEQc was re-synthesized on beads and further studied for its cell specificity, alanine scanning and site-directed deletion. The results showed that cNGQGEQc is specific for cell attachment to non-small cell lung cancer cells including A549, Calu-1 and H178, but not to other tumor cell lines. Both motif of -NGXG- and the length of six peptides are very important for A549 adhesion. Peptide cNGQGEQc labeled with FITC can specifically bind to A549 cell. In a blocking assay with anti-integrin antibodies（α1-6, αv/β1-5）, cell adhesion of A549 to peptide beads was obviously inhibited by integrin et3 combining with any β subunits. Results suggested that small molecule peptide cNGQGEQc can bind specifically to non-small cell lung cancer cell A549 via integrin α3 on cell surface.