Rational improvement of the affinity and selectivity of integrin binding of grafted lasso peptides

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

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

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 αvβ3 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).

Original languageEnglish
Pages (from-to)5829-5834
Number of pages6
JournalJournal of Medicinal Chemistry
Volume57
Issue number13
DOIs
StatePublished - 10 Jul 2014

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