2-Carba-lysophosphatidic acid is a novel β-lysophosphatidic acid analogue with high potential for lysophosphatidic acid receptor activation and autotaxin inhibition.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
30 08 2021
Historique:
received: 18 05 2021
accepted: 18 08 2021
entrez: 31 8 2021
pubmed: 1 9 2021
medline: 15 12 2021
Statut: epublish

Résumé

Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator that, along with its chemically stabilized analogue 2-carba-cyclic phosphatidic acid (2ccPA), induces various biological activities in vitro and in vivo. Although cPA is similar to lysophosphatidic acid (LPA) in structure and synthetic pathway, some of cPA biological functions apparently differ from those reported for LPA. We previously investigated the pharmacokinetic profile of 2ccPA, which was found to be rapidly degraded, especially in acidic conditions, yielding an unidentified compound. Thus, not only cPA but also its degradation compound may contribute to the biological activity of cPA, at least for 2ccPA. In this study, we determined the structure and examined the biological activities of 2-carba-lysophosphatidic acid (2carbaLPA) as a 2ccPA degradation compound, which is a type of β-LPA analogue. Similar to LPA and cPA, 2carbaLPA induced the phosphorylation of the extracellular signal-regulated kinase and showed potent agonism for all known LPA receptors (LPA

Identifiants

pubmed: 34462512
doi: 10.1038/s41598-021-96931-2
pii: 10.1038/s41598-021-96931-2
pmc: PMC8405639
doi:

Substances chimiques

Lysophospholipids 0
Receptors, Lysophosphatidic Acid 0
Recombinant Proteins 0
Solvents 0
Transforming Growth Factor alpha 0
Alcohol Oxidoreductases EC 1.1.-
choline oxidase EC 1.1.3.17
Phosphoric Diester Hydrolases EC 3.1.4.-
alkylglycerophosphoethanolamine phosphodiesterase EC 3.1.4.39
lysophosphatidic acid PG6M3969SG

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

17360

Informations de copyright

© 2021. The Author(s).

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Auteurs

Keiko Fukasawa (K)

Ochadai Academic Production, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, 112-8610, Japan.

Mari Gotoh (M)

Institute for Human Life Innovation, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, 112-8610, Japan. gotoh.mari@ocha.ac.jp.

Akiharu Uwamizu (A)

Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
AMED-LEAP and AMED-CREST, Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.

Takatsugu Hirokawa (T)

Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
Transborder Medical Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Masaki Ishikawa (M)

Clinical Omics Unit, Department of Applied Genomics, Kazusa DNA Research Institute, 2-5-23 Kazusa Kamatari, Kisarazu, Chiba, 292-0818, Japan.

Yoshibumi Shimizu (Y)

Ochadai Academic Production, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, 112-8610, Japan.
Laboratory of Racing Chemistry, 1731-2 Tsurutamachi Utsunomiya, Tochigi, 320-0851, Japan.

Shinji Yamamoto (S)

Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.

Kensuke Iwasa (K)

Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.

Keisuke Yoshikawa (K)

Department of Pharmacology, Faculty of Medicine, Saitama Medical University, 38 Moro-hongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.

Junken Aoki (J)

Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
AMED-LEAP and AMED-CREST, Japan Science and Technology Corporation, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.

Kimiko Murakami-Murofushi (K)

Ochadai Academic Production, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo, 112-8610, Japan. murofushi.kimiko@ocha.ac.jp.

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Classifications MeSH