| Autor: |
Kirberger SE; Department of Chemistry, University of Minnesota, 207 Pleasant St. SE., Minneapolis, MN 55455, USA. wcp@umn.edu., Ycas PD, Johnson JA, Chen C, Ciccone MF, Woo RWL, Urick AK, Zahid H, Shi K, Aihara H, McAllister SD, Kashani-Sabet M, Shi J, Dickson A, Dos Santos CO, Pomerantz WCK |
| Jazyk: |
angličtina |
| Zdroj: |
Organic & biomolecular chemistry [Org Biomol Chem] 2019 Feb 13; Vol. 17 (7), pp. 2020-2027. |
| DOI: |
10.1039/c8ob02599a |
| Abstrakt: |
Bromodomain and PHD finger containing protein transcription factor (BPTF) is an epigenetic protein involved in chromatin remodelling and is a potential anticancer target. The BPTF bromodomain has one reported small molecule inhibitor (AU1, rac-1). Here, advances made on the structure-activity relationship of a BPTF bromodomain ligand are reported using a combination of experimental and molecular dynamics simulations leading to the active enatiomer (S)-1. Additionally, a ligand deconstruction analysis was conducted to characterize important pharmacophores for engaging the BPTF bromodomain. These studies have been enabled by a protein-based fluorine NMR approach, highlighting the versatility of the method for selectivity, ligand deconstruction, and ligand binding. To enable future analysis of biological activity, cell growth analyses in a panel of cancer cell lines were carried out using CRISPR-Cas9 and (S)-1 to identify cell-based model systems that are sensitive to BPTF inhibition. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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