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Increasing αvβ3 Selectivity of the Anti-Angiogenic Drug Cilengitide by N-Methylation

Authors

  • Dr. Carlos Mas-Moruno,

    1. Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, 85747 Garching (Germany)
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  • Johannes G. Beck,

    1. Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, 85747 Garching (Germany)
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  • Dr. Lucas Doedens,

    1. Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, 85747 Garching (Germany)
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  • Dr. Andreas O. Frank,

    1. Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, 85747 Garching (Germany)
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  • Prof. Dr. Luciana Marinelli,

    1. Dipartimento di Chimica Farmaceutica e Tossicologica, Universitá di Napoli “Federico II”, 80131 Napoli (Italy)
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  • Dr. Sandro Cosconati,

    1. Dipartimento di Chimica Farmaceutica e Tossicologica, Universitá di Napoli “Federico II”, 80131 Napoli (Italy)
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  • Prof. Dr. Ettore Novellino,

    1. Dipartimento di Chimica Farmaceutica e Tossicologica, Universitá di Napoli “Federico II”, 80131 Napoli (Italy)
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  • Prof. Dr. Horst Kessler

    Corresponding author
    1. Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, 85747 Garching (Germany)
    2. Chemistry Department, Faculty of Science, King Abdulaziz University, 21589 Jeddah (Saudi Arabia)
    • Institute for Advanced Study and Center of Integrated Protein Science, Department Chemie, Technische Universität München, 85747 Garching (Germany)
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  • This work was partially supported by the International Graduate School of Science and Engineering. We thank B. Cordes for technical assistance with mass spectroscopy. C.M.M. thanks the Generalitat de Catalunya for a Beatriu de Pinós postdoctoral fellowship. J.G.B thanks the TUM Graduate School for support.

Abstract

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A subtle change: Structural changes upon amide bond methylation improve the selectivity of the anti-angiogenic drug Cilengitide, which after N-methylation at distinct positions discriminates between the closely related pro-angiogenic integrins αvβ3 and αvβ5 (see scheme).

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