Analysis of the critical structural determinant(s) of species-selective peroxisome proliferator-activated receptor alpha (PPARα)-activation by phenylpropanoic acid-type PPARα agonists

Hiroyuki Miyachi, Hideharu Uchiki

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In order to identify the critical structural feature(s) of phenylpropanoic acid-type PPARα agonists, such as KCL, which exhibit human peroxisome proliferator-activated receptor alpha (PPARα)-selective activation, transient transactivation assay of KCL and related derivatives was performed with PPARα containing wild-type and point-mutated (I272F or T279M) ligand-binding domain. The results indicated that the interaction of the distal hydrophobic tail part of KCL and related derivatives with amino acid residue 272 (isoleucine) in the helix three region of PPARα is of primary importance for human-selective PPARα activation.

Original languageEnglish
Pages (from-to)3145-3149
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number19
DOIs
Publication statusPublished - Oct 16 2003
Externally publishedYes

Fingerprint

PPAR alpha
Chemical activation
Acids
Derivatives
Isoleucine
Hydrophobic and Hydrophilic Interactions
Transcriptional Activation
Tail
Assays
Ligands
Amino Acids

ASJC Scopus subject areas

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

Cite this

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abstract = "In order to identify the critical structural feature(s) of phenylpropanoic acid-type PPARα agonists, such as KCL, which exhibit human peroxisome proliferator-activated receptor alpha (PPARα)-selective activation, transient transactivation assay of KCL and related derivatives was performed with PPARα containing wild-type and point-mutated (I272F or T279M) ligand-binding domain. The results indicated that the interaction of the distal hydrophobic tail part of KCL and related derivatives with amino acid residue 272 (isoleucine) in the helix three region of PPARα is of primary importance for human-selective PPARα activation.",
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AU - Uchiki, Hideharu

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AB - In order to identify the critical structural feature(s) of phenylpropanoic acid-type PPARα agonists, such as KCL, which exhibit human peroxisome proliferator-activated receptor alpha (PPARα)-selective activation, transient transactivation assay of KCL and related derivatives was performed with PPARα containing wild-type and point-mutated (I272F or T279M) ligand-binding domain. The results indicated that the interaction of the distal hydrophobic tail part of KCL and related derivatives with amino acid residue 272 (isoleucine) in the helix three region of PPARα is of primary importance for human-selective PPARα activation.

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