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Discovery of an artificial peptide agonist to the fibroblast growth factor receptor 1c/βKlotho complex from random peptide T7 phage display.

Abstract：

:Fibroblast growth factor receptor-1c (FGFR1c)/βKlotho (KLB) complex is a receptor of fibroblast growth factor 21 (FGF21). Pharmacologically, FGF21 shows anti-obesity and anti-diabetic effects upon peripheral administration. Here, we report the development of an artificial peptide agonist to the FGFR1c/KLB heterodimer complex. The peptide, F91-8A07 (LPGRTCREYPDLWWVRCY), was discovered from random peptide T7 phage display and selectively bound to the FGFR1c/KLB complex, but not to FGFR1c and KLB individually. After subsequent peptide dimerization using a short polyethyleneglycol (PEG) linker, the dimeric F91-8A07 peptide showed higher potent agonist activity than that of FGF21 in cultured primary human adipocytes. Moreover, the dimeric peptide led to an expression of the early growth response protein-1 (Egr-1) mRNA in vivo, which is a target gene of FGFR1c. To the best of our knowledge, this is the first report of a FGFR1c/KLB complex-selective artificial peptide agonist.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Sakamoto K,Kawata Y,Masuda Y,Umemoto T,Ito T,Asami T,Takekawa S,Ohtaki T,Inooka H

doi

10.1016/j.bbrc.2016.10.009

subject

Has Abstract

pub_date

2016-11-04 00:00:00

pages

55-60

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)31664-3

journal_volume

480

pub_type

杂志文章

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