PDBsum entry 3vso

Transcription

PDB id: 3vso

Contents

Protein chain

263 a.a.

Ligands

EK1

Waters ×117

PDB id:

3vso

Name:

Transcription

Title:

Human ppar gamma ligand binding domain in complex with a gamma selective agonist mekt21

Structure:

Peroxisome proliferator-activated receptor gamma. Chain: a, b. Fragment: ligand binding domain. Synonym: ppar-gamma, nuclear receptor subfamily 1 group c member 3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pparg, nr1c3. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.221 R-free: 0.257

Authors:

T.Oyama,T.Waku,M.Ohashi,K.Morikawa,H.Miyachi

Key ref:

M.Ohashi et al. (2013). Design and synthesis of a series of α-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved aqueous solubility. Bioorg Med Chem Lett, 21, 2319-2332. PubMed id: 23490155 DOI: 10.1016/j.bmc.2013.02.003

Date:

30-Apr-12 Release date: 01-May-13

Protein chains

P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma from Homo sapiens

Seq: 505 a.a.

Struc: 263 a.a.

DOI no: 10.1016/j.bmc.2013.02.003

Bioorg Med Chem Lett 21:2319-2332 (2013)

PubMed id: 23490155

Design and synthesis of a series of α-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved aqueous solubility.

M.Ohashi, T.Oyama, E.W.Putranto, T.Waku, H.Nobusada, K.Kataoka, K.Matsuno, M.Yashiro, K.Morikawa, N.H.Huh, H.Miyachi.

ABSTRACT

In the continuing study directed toward the development of peroxisome proliferator-activated receptor gamma (hPPARγ) agonist, we attempted to improve the water solubility of our previously developed hPPARγ-selective agonist 3, which is insufficiently soluble for practical use, by employing two strategies: introducing substituents to reduce its molecular planarity and decreasing its hydrophobicity via replacement of the adamantyl group with a heteroaromatic ring. The first approach proved ineffective, but the second was productive. Here, we report the design and synthesis of a series of α-benzyl phenylpropanoic acid-type hPPARγ partial agonists with improved aqueous solubility. Among them, we selected (R)-7j, which activates hPPARγ to the extent of about 65% of the maximum observed with a full agonist, for further evaluation. The ligand-binding mode and the reason for the partial-agonistic activity are discussed based on X-ray-determined structure of the complex of hPPARγ ligand-binding domain (LBD) and (R)-7j with previously reported ligand-LDB structures. Preliminal apoptotic effect of (R)-7j against human scirrhous gastric cancer cell line OCUM-2MD3 is also described.