Département de chimie, Université du Québec à Montréal, C.P. 8888, Succ. Centre-Ville, Montréal, Québec H3C 3P8, Canada.
Zenith Epigenetics Ltd, Suite 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada.
Bioorg Med Chem Lett. 2021 Sep 1;47:128208. doi: 10.1016/j.bmcl.2021.128208. Epub 2021 Jun 16.
BPTF (bromodomain and PHD finger containing transcription factor) is a multidomain protein that plays essential roles in transcriptional regulation, T-cell homeostasis and stem cell pluripotency. As part of the chromatin remodeling complex hNURF (nucleosome remodeling factor), BPTF epigenetic reader subunits are particularly important for BPTF cellular function. Here we report the synthesis of NVS-BPTF-1, a previously reported highly potent and selective BPTF-bromodomain inhibitor. Evaluation of the impact of the inhibition of BPTF-bromodomain using NVS-BPTF-1 on selected proteins involved in the antigen processing pathway revealed that exclusively targeting BPTF-bromodomain is insufficient to observe an increase of PSMB8, PSMB9, TAP1 and TAP2 proteins.
BPTF（含溴结构域和 PHD 指的转录因子）是一种多功能蛋白，在转录调控、T 细胞稳态和干细胞多能性中发挥着重要作用。作为染色质重塑复合物 hNURF（核小体重塑因子）的一部分，BPTF 表观遗传读取亚基对于 BPTF 的细胞功能尤为重要。在这里，我们报告了 NVS-BPTF-1 的合成，这是一种先前报道的高活性和选择性的 BPTF-溴结构域抑制剂。使用 NVS-BPTF-1 评估抑制 BPTF-溴结构域对参与抗原加工途径的选定蛋白质的影响表明，仅靶向 BPTF-溴结构域不足以观察到 PSMB8、PSMB9、TAP1 和 TAP2 蛋白的增加。
