Dataset Information

Design and Construction of a Focused DNA-Encoded Library for Multivalent Chromatin Reader Proteins.

ABSTRACT: Chromatin structure and function, and consequently cellular phenotype, is regulated in part by a network of chromatin-modifying enzymes that place post-translational modifications (PTMs) on histone tails. These marks serve as recruitment sites for other chromatin regulatory complexes that 'read' these PTMs. High-quality chemical probes that can block reader functions of proteins involved in chromatin regulation are important tools to improve our understanding of pathways involved in chromatin dynamics. Insight into the intricate system of chromatin PTMs and their context within the epigenome is also therapeutically important as misregulation of this complex system is implicated in numerous human diseases. Using computational methods, along with structure-based knowledge, we have designed and constructed a focused DNA-Encoded Library (DEL) containing approximately 60,000 compounds targeting bi-valent methyl-lysine (Kme) reader domains. Additionally, we have constructed DNA-barcoded control compounds to allow optimization of selection conditions using a model Kme reader domain. We anticipate that this target-class focused approach will serve as a new method for rapid discovery of inhibitors for multivalent chromatin reader domains.

SUBMITTER: Rectenwald JM

PROVIDER: S-EPMC7070942 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Design and Construction of a Focused DNA-Encoded Library for Multivalent Chromatin Reader Proteins.

Rectenwald Justin M JM Guduru Shiva Krishna Reddy SKR Dang Zhao Z Collins Leonard B LB Liao Yi-En YE Norris-Drouin Jacqueline L JL Cholensky Stephanie H SH Kaufmann Kyle W KW Hammond Scott M SM Kireev Dmitri B DB Frye Stephen V SV Pearce Kenneth H KH

Molecules (Basel, Switzerland) 20200222 4

Chromatin structure and function, and consequently cellular phenotype, is regulated in part by a network of chromatin-modifying enzymes that place post-translational modifications (PTMs) on histone tails. These marks serve as recruitment sites for other chromatin regulatory complexes that 'read' these PTMs. High-quality chemical probes that can block reader functions of proteins involved in chromatin regulation are important tools to improve our understanding of pathways involved in chromatin dy ...[more]

PMID: 32098353

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Dataset Information

Design and Construction of a Focused DNA-Encoded Library for Multivalent Chromatin Reader Proteins.

Publications

Design and Construction of a Focused DNA-Encoded Library for Multivalent Chromatin Reader Proteins.

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