TY - JOUR
T1 - Structure–activity relationship study at C9 position of kaitocephalin
AU - Yasuno, Yoko
AU - Hamada, Makoto
AU - Yoshida, Yuya
AU - Shimamoto, Keiko
AU - Shigeri, Yasushi
AU - Akizawa, Toshifumi
AU - Konishi, Motomi
AU - Ohfune, Yasufumi
AU - Shinada, Tetsuro
N1 - Funding Information:
TS gratefully thanks to financial supports from Scientific Research of Innovative Areas, Chemical Biology of Natural Products, the Ministry of Education, Culture, Sports, Science and Technology (No. 23102009) and the Japan Society for the Promotion of Science (KAKENHI Nos. 23228001, 25282233). YY gratefully thanks to financial supports by the Sasagawa Scientific Research Grant from The Japan Science Society.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bmcl.2016.06.026
DO - 10.1016/j.bmcl.2016.06.026
M3 - Article
C2 - 27329796
AN - SCOPUS:84977599971
VL - 26
SP - 3543
EP - 3546
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 15
ER -