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

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...

Full description

Saved in:
Bibliographic Details
Published in:Chemical science (Cambridge) 2017-10, Vol.8 (10), p.6959-6963
Main Authors: Kitahata, S, Yakushiji, F, Ichikawa, S
Format: Article
Language:English
Subjects:
Chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2041-6520
2041-6539
DOI:10.1039/c7sc02941a