Rational Improvement of the Affinity and Selectivity of Integrin Binding of Grafted Lasso Peptides

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• 作者：Julian D. Hegemann ; Mariarosaria De Simone ; Marcel Zimmermann ; Thomas A. Knappe ; Xiulan Xie ; Francesco Saverio Di Leva ; Luciana Marinelli ; Ettore Novellino ; Stefan Zahler ; Horst Kessler ; Mohamed A. Marahiel
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：July 10, 2014
• 年：2014
• 卷：57
• 期：13
• 页码：5829-5834
• 全文大小：336K
• ISSN：1520-4804

文摘

Integrins moderate diverse important functions in the human body and are promising targets in cancer therapy. Hence, the selective inhibition of specific integrins is of great medicinal interest. Here, we report the optimization of a grafted lasso peptide, yielding MccJ25(RGDF), which is a highly potent and selective 伪v尾3 integrin inhibitor. Furthermore, its NMR structure was elucidated and employed in a molecular dynamics approach, revealing information about the integrin binding mode and selectivity profile of MccJ25(RGDF).