Nutrient-Based Chemical Library as a Source of Energy
Metabolism Modulators
Posted on 2019-08-25 - 12:30
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.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Furuta, Tomoyuki; Mizukami, Yuya; Asano, Lisa; Kotake, Kenjiro; Ziegler, Slava; Yoshida, Hiroki; et al. (2019). Nutrient-Based Chemical Library as a Source of Energy
Metabolism Modulators. ACS Publications. Collection. https://doi.org/10.1021/acschembio.9b00444
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (11)
TF
Tomoyuki Furuta
YM
Yuya Mizukami
LA
Lisa Asano
KK
Kenjiro Kotake
SZ
Slava Ziegler
HY
Hiroki Yoshida
MW
Mizuki Watanabe
SS
Shin-ichi Sato
HW
Herbert Waldmann
MN
Makiya Nishikawa
MU
Motonari Uesugi