TY - JOUR
T1 - Hes1-Binding Compounds Isolated by Target Protein Oriented Natural Products Isolation (TPO-NAPI)
AU - Arai, Midori A.
AU - Tanaka, Mitsuha
AU - Tanouchi, Kana
AU - Ishikawa, Naoki
AU - Ahmed, Firoj
AU - Sadhu, Samir K.
AU - Ishibashi, Masami
N1 - Funding Information:
We thank Professor Tohru Gonoi (Medical Mycology Research Center, Chiba University) for the identification of Micromonospora sp. IFM 11769. This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS), a Grant-in-Aid for Scientific Research on Innovative Areas “Chemical Biology of Natural Products” from the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT), and by a Workshop on Chirality at Chiba University (WCCU). This work was inspired by the international and interdisciplinary environments of the JSPS Core-to-Core Program “Asian Chemical Biology Initiative”.
Publisher Copyright:
© 2017 The American Chemical Society and American Society of Pharmacognosy.
PY - 2017/2/24
Y1 - 2017/2/24
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jnatprod.6b01072
DO - 10.1021/acs.jnatprod.6b01072
M3 - Article
C2 - 28191975
AN - SCOPUS:85013777154
SN - 0163-3864
VL - 80
SP - 538
EP - 543
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 2
ER -