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Title: Nutrient-Based Chemical Library as a Source of Energy Metabolism Modulators
Authors: Furuta, Tomoyuki
Mizukami, Yuya
Asano, Lisa
Kotake, Kenjiro
Ziegler, Slava
Yoshida, Hiroki
Watanabe, Mizuki
Sato, Shin-ichi
Waldmann, Herbert
Nishikawa, Makiya
Uesugi, Motonari  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 西川, 元也
上杉, 志成
Keywords: Molecular Medicine
General Medicine
Issue Date: 20-Sep-2019
Publisher: American Chemical Society (ACS)
Journal title: ACS Chemical Biology
Volume: 14
Issue: 9
Start page: 1860
End page: 1865
Abstract: Covalent conjugates of multiple nutrients often exhibit greater biological activities than each individual nutrient and more predictable safety profiles than completely unnatural chemical entities. Here, we report the construction and application of a focused chemical library of 308 covalent conjugates of a variety of small-molecule nutrients. Screening of the library with a reporter gene of sterol regulatory element-binding protein (SREBP), a master regulator of mammalian lipogenesis, led to the discovery of a conjugate of docosahexaenoic acid (DHA), glucosamine, and amino acids as an inhibitor of SREBP (molecule 1, DHG). Mechanistic analyses indicate that molecule 1 impairs the SREBP activity by inhibiting glucose transporters and thereby activating AMP-activated protein kinase (AMPK). Oral administration of molecule 1 suppressed the intestinal absorption of glucose in mice. These results suggest that such synthetic libraries of nutrient conjugates serve as a source of novel chemical tools and pharmaceutical seeds that modulate energy metabolism.
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in 'ACS Chemical Biology', copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
The full-text file will be made open to the public on 22 August 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1021/acschembio.9b00444
PubMed ID: 31436407
Appears in Collections:Journal Articles

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