Design, Synthesis, and Characterization of a Fluorescence Polarization Pan-BET Bromodomain Probe

Carolyn N. Paulson; Xianghong Guan; Alex M. Ayoub; Alice Chan; Rezaul M. Karim; William C.K. Pomerantz; Ernst Schönbrunn; Gunda I. Georg; Jon E. Hawkinson

doi:10.1021/acsmedchemlett.8b00380

Design, Synthesis, and Characterization of a Fluorescence Polarization Pan-BET Bromodomain Probe

Carolyn N. Paulson, Xianghong Guan, Alex M. Ayoub, Alice Chan, Rezaul M. Karim, William C.K. Pomerantz, Ernst Schönbrunn, Gunda I. Georg, Jon E. Hawkinson

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Several chemical probes have been developed for use in fluorescence polarization screening assays to aid in drug discovery for the bromodomain and extra-terminal domain (BET) proteins. However, few of those have been characterized in the literature. We have designed, synthesized, and thoroughly characterized a novel fluorescence polarization pan-BET chemical probe suitable for high-throughput screening, structure-activity relationships, and hit-to-lead potency and selectivity assays to identify and characterize BET bromodomain inhibitors.

Original language	English (US)
Pages (from-to)	1223-1229
Number of pages	7
Journal	ACS Medicinal Chemistry Letters
Volume	9
Issue number	12
DOIs	https://doi.org/10.1021/acsmedchemlett.8b00380
State	Published - Dec 13 2018

Bibliographical note

Funding Information:
*E-mail: hawkinso@umn.edu. *E-mail: georg@umn.edu. ORCID William C. K. Pomerantz: 0000-0002-0163-4078 Ernst Schönbrunn: 0000-0002-3589-3510 Gunda I. Georg: 0000-0002-8900-9460 Jon E. Hawkinson: 0000-0001-5461-7071 Author Contributions ⊥These authors contributed equally. All authors have given approval to the final version of the manuscript. Funding Financial support for this project is gratefully acknowledged from the NICHD (HHSN27520130001 and 1 U54 HD09354) and NSF-CAREER Award CHE-1352091. Notes The authors declare no competing financial interest.

Publisher Copyright:
© 2018 American Chemical Society.

Keywords

BET
bromodomain and extra-terminal domain
fluorescence polarization
pan-BET probe

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295860

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abstract = "Several chemical probes have been developed for use in fluorescence polarization screening assays to aid in drug discovery for the bromodomain and extra-terminal domain (BET) proteins. However, few of those have been characterized in the literature. We have designed, synthesized, and thoroughly characterized a novel fluorescence polarization pan-BET chemical probe suitable for high-throughput screening, structure-activity relationships, and hit-to-lead potency and selectivity assays to identify and characterize BET bromodomain inhibitors.",

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AU - Chan, Alice

AU - Karim, Rezaul M.

AU - Pomerantz, William C.K.

AU - Schönbrunn, Ernst

AU - Georg, Gunda I.

AU - Hawkinson, Jon E.

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Design, Synthesis, and Characterization of a Fluorescence Polarization Pan-BET Bromodomain Probe

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