Structure–activity relationship study at C9 position of kaitocephalin

Yoko Yasuno, Makoto Hamada, Yuya Yoshida, Keiko Shimamoto, Yasushi Shigeri, Toshifumi Akizawa, Motomi Konishi, Yasufumi Ohfune, Tetsuro Shinada

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Kaitocephalin (KCP) isolated from Eupenicillium shearii PF1191 is an unusual amino acid natural product in which serine, proline, and alanine moieties are liked with carbon–carbon bonds. KCP exhibits potent and selective binding affinity for one of the ionotropic glutamate receptor subtypes, NMDA receptors (Ki= 7.8 nM). In this study, new structure–activity relationship studies at C9 of KCP were implemented. Eleven new KCP analogs with different substituents at C9 were prepared and employed for binding affinity tests using native ionotropic glutamate receptors. Replacement of the 3,5-dichloro-4-hydroxybenzoyl group of KCP with a 3-phenylpropionyl group resulted in significant loss of binding affinity for NMDARs (Ki= 1300 nM), indicating an indispensable role of the aromatic ring of KCP in the potent and selective binding to NMDARs. Other analogs showed potent binding affinity in a range of 11–270 nM. These findings would directly link to develop useful chemical tools toward imaging and labeling of NMDARs.

Original languageEnglish
Pages (from-to)3543-3546
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number15
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

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

Cite this

Yasuno, Y., Hamada, M., Yoshida, Y., Shimamoto, K., Shigeri, Y., Akizawa, T., ... Shinada, T. (2016). Structure–activity relationship study at C9 position of kaitocephalin. Bioorganic and Medicinal Chemistry Letters, 26(15), 3543-3546. https://doi.org/10.1016/j.bmcl.2016.06.026