一种特异性识别小细胞肺癌细胞的小分子肽

应用“一个珠子一个化合物”的组合化学肽库技术,筛选得到特异性识别小细胞肺癌细胞(DMS53)的小分子肽.初次筛选共得到32个与DMS53阳性结合的珠子,经氨基酸序列分析后发现,含有cNGRXXXc或cXNGRXXc肽链结构的序列共有10个.再次合成三种有代表性的小分子肽,发现cFNGRQQc与DMS53的结合率明显高于其他小分子肽.选择cFNGRQQc作进一步的细胞特异性研究,发现cFNGRQQc与DMS53的粘附特异性明显高于其他细胞系,对cFNGRQQc的结构分析显示,-NGR-及六肽长度对小分子肽与DMS53细胞的粘附非常重要.用抗整合素、E-cadherin、NCAM及ICAM的抗体或多肽阻断小分子肽与DMS53细胞表面的相应受体结合,未见明显的阻断效应.小分子肽与DMS53细胞表面的结合位点有待于进一步证实.

A Novel Specific Small Molecule Peptide for Small Cell Lung Cancer

Screen small molecule peptide specific binding to small cell lung cancer cell (DMS53) was screened by using the "one-bead one-peptide" combinatorial technology. Thirty two positive beads binding to DMS53 were totally obtained after primary screening. Consensus peptide sequences of cXNGRXXc and cNGRXXXc were identified by amino acid sequencing in ten beads. Three representative peptides were re-synthesized on beads. Secondary screening showed that cell adhesion percentage of cFNGRQQc to DMSS was higher than the other two peptides. cFNGRQQc was further studied for cell specificity, alanine scanning and site-directed deletion. The results showed that cFNGRQQc is specific for promoting cell adhesion to DMS53 but not to other human cell lines. Both motif of -NGR- and the length of six peptide of cFNGRQQc structure are important for DMS53 attachment. In an antibody or peptide blocking assay, cell adhesion of DMS53 to peptide bead was not inhibited by antibodies or peptides including anti-integrin, E-cadherin, NCAM and ICAM. The binding site on DMS53 surface for cFNGRQQc peptide need to be proven in the future.