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

Shintaro Ban, Takuji Oyama, Jun Ichi Kasuga, Kenji Ohgane, Yoshino Nishio, Kosuke Morikawa, Yuichi Hashimoto, Hiroyuki Miyachi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Based on X-ray crystallographic analysis of a peroxisome proliferator-activated receptor (PPAR) α/δ dual agonist complexed with human PPARs ligand binding domain (LBD), we previously reported the design and synthesis of a pyrene-based fluorescent PPARα/δ co-agonist 2. Here, we found that the fluorescence intensity of 2 increased upon binding to hPPARα-LBD, in a manner dependent upon the concentration of the LBD. But, surprisingly, the fluorescence intensity of 2 decreased concentration- dependently upon binding to hPPRδ-LBD. Site-directed mutagenesis of the two hPPAR subtypes clearly indicated that Trp264 of hPPARδ-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 hPPARδ-LBD.

Original languageEnglish
Pages (from-to)3460-3464
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume20
Issue number11
DOIs
Publication statusPublished - Jun 1 2012

Keywords

  • Fluorescent PPARα/δ co-agonist
  • PPARα
  • PPARδ
  • Peroxisome proliferator-activated receptor
  • Site-directed mutagenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Bidirectional fluorescence properties of pyrene-based peroxisome proliferator-activated receptor (PPAR) α/δ dual agonist'. Together they form a unique fingerprint.

Cite this