New cyclic tetrapeptides from Nonomuraea sp. TA-0426 that inhibit glycine transporter type 1 (GlyT1)

Yuichi Terui; Yi-wen Chu; Jun-ying Li; Tsutomu Ando; Takuya Fukunaga; Takeshi Aoki; Yoshihisa Toda

doi:10.1016/j.bmcl.2008.10.104

New cyclic tetrapeptides from Nonomuraea sp. TA-0426 that inhibit glycine transporter type 1 (GlyT1)

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6321-3. doi: 10.1016/j.bmcl.2008.10.104. Epub 2008 Oct 26.

Authors

Yuichi Terui¹, Yi-wen Chu, Jun-ying Li, Tsutomu Ando, Takuya Fukunaga, Takeshi Aoki, Yoshihisa Toda

Affiliation

¹ Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan. yuichi.terui@po.rd.taisho.co.jp

PMID: 19013063
DOI: 10.1016/j.bmcl.2008.10.104

Abstract

In the course of our search for natural antipsychotic agents, we isolated five new cyclic tetrapeptides from the fermentation broth of Nonomuraea sp. TA-0426. These compounds turned out to be analogues of WSS2220, which had been produced by the same actinomycete and showed strong inhibitory activity against GlyT1. Four of the present peptides exhibit more potent GlyT1 inhibitory activities than WSS2220.

MeSH terms

Actinomyces / metabolism*
Antipsychotic Agents / chemical synthesis
Antipsychotic Agents / pharmacology*
Cell Line, Tumor
Dose-Response Relationship, Drug
Glycine / chemistry*
Glycine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Glycine Plasma Membrane Transport Proteins / chemistry*
Humans
Inhibitory Concentration 50
Isoleucine / chemistry
Magnetic Resonance Spectroscopy
Methylation
Models, Chemical
Peptides / chemistry*
Structure-Activity Relationship
Time Factors

Substances

Antipsychotic Agents
Glycine Plasma Membrane Transport Proteins
Peptides
Isoleucine
Glycine