Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography

被引：35

作者：

Guetzoyan, Lucie ^{[1
]}

Ingham, Richard J. ^{[1
]}

Nikbin, Nikzad ^{[1
]}

Rossignol, Julien ^{[1
]}

Wolling, Michael ^{[1
]}

Baumert, Mark ^{[2
]}

Burgess-Brown, Nicola A. ^{[3
]}

Strain-Damerell, Claire M. ^{[3
]}

Shrestha, Leela ^{[3
]}

Brennan, Paul E. ^{[3
]}

Fedorov, Oleg ^{[3
]}

Knapp, Stefan ^{[3
]}

Ley, Steven V. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Chem, Innovat Technol Ctr, Cambridge CB2 1EW, England

[2] Advion Ltd, Harlow Enterprise Hub, Harlow CM20 2NQ, Essex, England

[3] Univ Oxford, Nuffield Dept Med, Struct Genom Consortium & Target Discovery Inst, Oxford OX3 7FZ, England

来源：

MEDCHEMCOMM | 2014年 / 5卷 / 04期

基金：

英国工程与自然科学研究理事会;

关键词：

BET BROMODOMAINS; INHIBITORS; DISCOVERY; RECOGNITION; TECHNOLOGY; REACTOR; LIGAND;

D O I：

10.1039/c4md00007b

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A combination of conventional organic synthesis, remotely monitored flow synthesis and bioassay platforms, were used for the evaluation of novel inhibitors targeting bromodomains outside the well-studied bromodomain and extra terminal (BET) family, here exemplified by activity measurements on the bromodomain of BRD9 protein, a component of some tissue-specific SWi/SNF chromatin remodelling complexes. The Frontal Affinity Chromatography combined with Mass Spectrometry (FAC-MS) method proved to be reliable and results correlated well with an independent thermal shift assay.

引用

页码：540 / 546

页数：7

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