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Multifunctional αvβ6 Integrin-Specific Peptide–Pt(IV) Conjugates for Cancer Cell Targeting
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2017-08-10 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00421 Anne C Conibear 1 , Sonja Hager 2 , Josef Mayr 3 , Matthias H M Klose 3 , Bernhard K Keppler 3 , Christian R Kowol 3 , Petra Heffeter 2 , Christian F W Becker 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2017-08-10 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00421 Anne C Conibear 1 , Sonja Hager 2 , Josef Mayr 3 , Matthias H M Klose 3 , Bernhard K Keppler 3 , Christian R Kowol 3 , Petra Heffeter 2 , Christian F W Becker 1
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Increasing the specificity of cancer therapy, and thereby decreasing damage to normal cells, requires targeting to cancer-cell specific features. The αvβ6 integrin is a receptor involved in cell adhesion and is frequently up-regulated in cancer cells compared to normal cells. We have selected a peptide ligand reported to bind specifically to the β6 integrin and have synthesized a suite of multispecific molecules to explore the potential for targeting of cancer cells. A combination of solid-phase peptide synthesis and chemoselective ligations was used to synthesize multifunctional molecules composed of integrin-targeting peptides, cytotoxic platinum(IV) prodrugs, and fluorescent or affinity probes joined with flexible linkers. The modular synthesis approach facilitates the construction of peptide–drug conjugates with various valencies and properties in a convergent manner. The binding and specificity of the multifunctional peptide conjugates were investigated using a cell line transfected with the β6 integrin and fluorescence microscopy. This versatile and highly controlled approach to synthesizing labeled peptide–drug conjugates has the potential to target potent cytotoxic drugs specifically to cancer cells, reducing the doses required for effective treatment.
中文翻译：
用于癌细胞靶向的多功能 αvβ6 整合素特异性肽-Pt(IV) 偶联物
增加癌症治疗的特异性，从而减少对正常细胞的损伤，需要针对癌细胞的特异性特征。α v β 6整合素是一种参与细胞粘附的受体，与正常细胞相比，它在癌细胞中经常上调。我们选择了一种据报道可与 β 6特异性结合的肽配体整合素并合成了一套多特异性分子来探索靶向癌细胞的潜力。固相肽合成和化学选择性连接的组合用于合成由整合素靶向肽、细胞毒性铂 (IV) 前药和荧光或亲和探针与柔性接头组成的多功能分子。模块化合成方法有助于以收敛的方式构建具有各种化合价和性质的肽-药物偶联物。使用转染 β 6的细胞系研究多功能肽缀合物的结合和特异性整合素和荧光显微镜。这种合成标记肽-药物偶联物的多功能且高度可控的方法有可能将强效细胞毒性药物特异性靶向癌细胞，从而减少有效治疗所需的剂量。
更新日期：2017-08-10
中文翻译：
用于癌细胞靶向的多功能 αvβ6 整合素特异性肽-Pt(IV) 偶联物
增加癌症治疗的特异性，从而减少对正常细胞的损伤，需要针对癌细胞的特异性特征。α v β 6整合素是一种参与细胞粘附的受体，与正常细胞相比，它在癌细胞中经常上调。我们选择了一种据报道可与 β 6特异性结合的肽配体整合素并合成了一套多特异性分子来探索靶向癌细胞的潜力。固相肽合成和化学选择性连接的组合用于合成由整合素靶向肽、细胞毒性铂 (IV) 前药和荧光或亲和探针与柔性接头组成的多功能分子。模块化合成方法有助于以收敛的方式构建具有各种化合价和性质的肽-药物偶联物。使用转染 β 6的细胞系研究多功能肽缀合物的结合和特异性整合素和荧光显微镜。这种合成标记肽-药物偶联物的多功能且高度可控的方法有可能将强效细胞毒性药物特异性靶向癌细胞，从而减少有效治疗所需的剂量。
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