Selective Fragments for the CREBBP Bromodomain Identified from an Encoded Self‐assembly Chemical Library


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Date

2020-09-16

Publication Type

Journal Article

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Abstract

DNA‐encoded chemical libraries (DECLs) are collections of chemical moieties individually coupled to distinctive DNA barcodes. Compounds can be displayed either at the end of a single DNA strand (i. e., single‐pharmacophore libraries) or at the extremities of two complementary DNA strands (i. e., dual‐pharmacophore libraries). In this work, we describe the use of a dual‐pharmacophore encoded self‐assembly chemical (ESAC) library for the affinity maturation of a known 4,5‐dihydrobenzodiazepinone ring (THBD) acetyl‐lysine (KAc) mimic for the cyclic‐AMP response element binding protein (CREB) binding protein (CREBBP or CBP) bromodomain. The new pair of fragments discovered from library selection showed a sub‐micromolar affinity for the CREBBP bromodomain in fluorescence polarization and ELISA assays, and selectivity against BRD4(1). © 2020 Wiley-VCH GmbH.

Publication status

published

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Book title

Journal / series

Volume

15 (18)

Pages / Article No.

1752 - 1756

Publisher

Wiley

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Edition / version

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Geographic location

Date collected

Date created

Subject

CREBBP bromodomain; DNA-encoded chemical library; Encoded self-assembly chemical library; Inhibitors; Medicinal chemistry

Organisational unit

03463 - Neri, Dario (ehemalig) / Neri, Dario (former) check_circle
08641 - Scheuermann, Jörg (Tit.-Prof.) / Scheuermann, Jörg (Tit.-Prof.)

Notes

Funding

182003 - Understanding and Exploiting the Molecular Targeting of Tumor Neo-vasculature (SNF)

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