Issue 10, 2017

Impact of the structures of macrocyclic Michael acceptors on covalent proteasome inhibition

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

Supplementary files

Article information

Article type
Edge Article
Submitted
05 Jul 2017
Accepted
10 Aug 2017
First published
11 Aug 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 6959-6963

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

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements