Multifunctional α(v)β(6) Integrin-Specific Peptide-Pt(IV) Conjugates for Cancer Cell Targeting.
Multifunctional α(v)β(6) Integrin-Specific Peptide-Pt(IV) Conjugates for Cancer Cell Targeting.
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DOI：
10.1021/acs.bioconjchem.7b00421
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发表时间：
2017-09-20
影响因子：
4.7
通讯作者：
Becker CFW
中科院分区：
文献类型：
--
作者：
Conibear AC;Hager S;Mayr J;Klose MHM;Keppler BK;Kowol CR;Heffeter P;Becker CFW
增加癌症治疗的特异性，从而减少对正常细胞的损伤，需要靶向癌细胞的特异性特征。αvβ6整联蛋白是一种参与细胞粘附的受体，与正常细胞相比，在癌细胞中经常上调。我们选择了一个肽配体，据报道，特异性结合β6整合素，并合成了一套多特异性分子，以探索潜在的靶向癌细胞。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）前药和与柔性接头连接的荧光或亲和探针组成的多功能分子。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-药物缀合物。使用用β6整联蛋白转染的细胞系和荧光显微镜研究多功能肽缀合物的结合和特异性。这种合成标记的肽-药物缀合物的通用且高度受控的方法具有将有效的细胞毒性药物特异性靶向癌细胞的潜力，从而降低有效治疗所需的剂量。
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.
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影响因子：
4.7
作者：
Agarwal, Paresh;Bertozzi, Carolyn R.
通讯作者：
Bertozzi, Carolyn R.
影响因子：
4.9
作者：
Hallam, Trevor J.;Wold, Erik;Smider, Vaughn V.
通讯作者：
Smider, Vaughn V.
DOI：
10.1002/anie.201603488
发表时间：
2016-08-16
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Cox N;Kintzing JR;Smith M;Grant GA;Cochran JR
通讯作者：
Cochran JR
影响因子：
2.8
作者：
Mas-Moruno C;Rechenmacher F;Kessler H
通讯作者：
Kessler H
影响因子：
5.8
作者：
Heffeter, P.;Jakupec, M. A.;Koerner, W.;Chiba, P.;Pirker, C.;Dornetshuber, R.;Elbling, L.;Sutterluety, H.;Micksche, M.;Keppler, B. K.;Berger, W.
通讯作者：
Berger, W.