Bidirectional fluorescence properties of pyrene-based peroxisome proliferator-activated receptor (PPAR) α/δ dual agonist

被引：6

作者：

Ban, Shintaro ^{[1
]}

Oyama, Takuji ^{[2
]}

Kasuga, Jun-ichi ^{[3
]}

Ohgane, Kenji ^{[3
]}

Nishio, Yoshino ^{[1
]}

Morikawa, Kosuke ^{[4
]}

Hashimoto, Yuichi ^{[3
]}

Miyachi, Hiroyuki ^{[1
]}

机构：

[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Kita Ku, Okayama 7008530, Japan

[2] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan

[3] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan

[4] Int Inst Adv Studies, Kizugawa, Kyoto 6190225, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 11期

关键词：

Peroxisome proliferator-activated receptor; PPAR delta; PPAR alpha; Fluorescent PPAR alpha/delta co-agonist; Site-directed mutagenesis; ADIPOSE; DESIGN; GAMMA; ASSAY;

D O I：

10.1016/j.bmc.2012.04.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Based on X-ray crystallographic analysis of a peroxisome proliferator-activated receptor (PPAR) alpha/delta dual agonist complexed with human PPARs ligand binding domain (LBD), we previously reported the design and synthesis of a pyrene-based fluorescent PPAR alpha/delta co-agonist 2. Here, we found that the fluorescence intensity of 2 increased upon binding to hPPAR alpha-LBD, in a manner dependent upon the concentration of the LBD. But, surprisingly, the fluorescence intensity of 2 decreased concentration-dependently upon binding to hPPR delta-LBD. Site-directed mutagenesis of the two hPPAR subtypes clearly indicated that Trp264 of hPPAR delta-LBD, located between H2' helix and H3 helix (omega loop), is critical for the concentration-dependent decrease in fluorescence intensity, which is suggested to be due to fluorescence resonance energy transfer (FRET) from the pyrene moiety of bound 2 to the nearby side-chain indole moiety of Trp264 in the hPPAR delta-LBD. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：3460 / 3464

页数：5

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