通过靶向蛋白导向天然产物分离（TPO-NAPI）分离的 Hes1 结合化合物。

Hes1-Binding Compounds Isolated by Target Protein Oriented Natural Products Isolation (TPO-NAPI).

机构信息

Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

Department of Pharmaceutical Chemistry, University of Dhaka , Dhaka1000, Bangladesh.

出版信息

J Nat Prod. 2017 Feb 24;80(2):538-543. doi: 10.1021/acs.jnatprod.6b01072. Epub 2017 Feb 13.

DOI:10.1021/acs.jnatprod.6b01072

PMID:28191975

Abstract

Hairy and enhancer of split 1 (Hes1) is a transcription factor that acts in neural stem cells to inhibit differentiation. We recently developed target protein oriented natural products isolation (TPO-NAPI) using Hes1-immobilized beads to identify activators of neural stem cells. Isomicromonolactam (1), staurosporin (2), and linarin (3) were isolated as Hes1-binding compounds using the TPO-NAPI method. Of these, compound 1 enhanced neural stem cell differentiation. Using truncated Hes1 proteins, the binding region of Hes1 for 1 was estimated to be in the C-terminal half that includes a TLE/Grg binding site. The differentiation-promoting activity of inohanamine (4) is also reported.

摘要

Hairy 和增强子的分裂 1（Hes1）是一种转录因子，它在神经干细胞中起作用，抑制分化。我们最近使用 Hes1 固定珠开发了针对靶蛋白的天然产物分离（TPO-NAPI）方法，以鉴定神经干细胞的激活剂。Isomicromonolactam（1）、staurosporin（2）和 linarin（3）被分离为 Hes1 结合化合物使用 TPO-NAPI 方法。其中，化合物 1 增强了神经干细胞的分化。使用截短的 Hes1 蛋白，估计 Hes1 与 1 的结合区域在包含 TLE/Grg 结合位点的 C 端半部分。也报道了 inohanamine（4）的促分化活性。