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Issue 10, 2017
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Impact of the structures of macrocyclic Michael acceptors on covalent proteasome inhibition

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Abstract

Molecules that have a reactive functional group within a macrocycle represent a class of covalent inhibitor. The relationship between reactivity and affinity for the target is cooperative and complicated. An understanding and characterization of this class of inhibitor are vital for the development of covalent inhibitors as drug candidates. Herein, we describe a systematic analysis of structure–activity relationships using a series of syringolin analogues, which are irreversible covalent inhibitors of proteasomes. We investigate the detailed mechanistic effects of the macrocycles on affinity and reaction rate.

Graphical abstract: Impact of the structures of macrocyclic Michael acceptors on covalent proteasome inhibition

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Publication details

The article was received on 05 Jul 2017, accepted on 10 Aug 2017 and first published on 11 Aug 2017


Article type: Edge Article
DOI: 10.1039/C7SC02941A
Citation: Chem. Sci., 2017,8, 6959-6963
  • Open access: Creative Commons BY license
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    Impact of the structures of macrocyclic Michael acceptors on covalent proteasome inhibition

    S. Kitahata, F. Yakushiji and S. Ichikawa, Chem. Sci., 2017, 8, 6959
    DOI: 10.1039/C7SC02941A

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