N-Methylation of isoDGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent,Journal of Medicinal Chemistry

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N-Methylation of isoDGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2018-02-28 00:00:00 , DOI: 10.1021/acs.jmedchem.7b01752
Tobias G. Kapp ₁ , Francesco Saverio Di Leva ₂ , Johannes Notni ₃ , Andreas F. B. Räder ₁ , Maximilian Fottner ₁ , Florian Reichart ₁ , Dominik Reich ₃ , Alexander Wurzer ₃ , Katja Steiger ₄ , Ettore Novellino ₂ , Udaya Kiran Marelli ₅ , Hans-Jürgen Wester ₃ , Luciana Marinelli ₂ , Horst Kessler ₁

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Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg-isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg-isoDGR-(NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg-isoDGR-(NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring α5β1 integrin expression in a M21 mouse xenograft.

中文翻译：

iso DGR肽的N-甲基化：选择性α5β1-整联蛋白配体作为有效的肿瘤成像剂的发现。

整联蛋白亚型α5β1的特异性靶向在癌症的诊断和治疗中具有很高的潜力。通过连续的N-甲基化，我们成功地将双选择性α5β1/αvβ6肽c（phg - iso DGR-k）转化为有效的肽RGD结合α5β1亚型选择性配体c（phg- iso DGR-（N Me）k）。核磁共振波谱学和分子模型阐明了其改进的选择性分布的分子基础。为了证明其在体内的潜力，c（phg- iso DGR-（NMe）k）用螯合剂TRAP进行了三聚，并用作正电子发射断层扫描示踪剂，以监测M21小鼠异种移植物中α5β1整联蛋白的表达。

更新日期：2018-02-28

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