Development of Novel Ligands for Glutamate Receptors Using Natural Neurotoxins as the Structural Motif

Kaitocephalin因其对哺乳动物中枢神经系统谷氨酸受体的拮抗作用而备受关注，有望成为研究谷氨酸受体功能的有力工具和开发神经保护剂的先导。本研究实现了kaitocephalin的高效全合成，并开发了新的合成方法。我们还合成了其衍生物、结构类似物和其他神经活性氨基酸，其SAR研究表明，kaitocephalin及其部分衍生物显示出与NMDA受体的强结合活性。

Kaitocephalin has attracted much attention due to its potent antagonist activity to glutamate receptors in mammalian CNS, and is expected to be a potent candidate as a tool to investigate the function of glutamate receptors as well as a leadto develop neuroprotecting agent. In this study, we have achieved the highly efficient total synthesis of kaitocephalin which was accompanied by the development of new synthetic methods. We also performed the synthesis of its derivatives, structurally simplifiedanalogs, and other neuroactive amino acids, whose SAR studies revealed that kaitocephalin and some of its derivatives exhibited potent binding activities to NMDA receptors.