基于2-氨基己二酸-C(O)-谷氨酸的前列腺特异性膜抗原配体，有望用作诊疗药物。
2-Aminoadipic Acid-C(O)-Glutamate Based Prostate-Specific Membrane Antigen Ligands for Potential Use as Theranostics.
作者信息
Nakajima Ryo, Nováková Zora, Tueckmantel Werner, Motlová Lucia, Bařinka Cyril, Kozikowski Alan P
机构信息
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic.
出版信息
ACS Med Chem Lett. 2018 Oct 24;9(11):1099-1104. doi: 10.1021/acsmedchemlett.8b00318. eCollection 2018 Nov 8.
Abstract
The design and synthesis of prostate specific membrane antigen (PSMA) ligands derived from 2-aminoadipic acid, a building block that has not previously been used to construct PSMA ligands, are reported. The effects of both the linker length and of an N-substituent of our PSMA ligands were probed, and X-ray structures of five of these ligands bound to PSMA were obtained. Among the ligands disclosed herein, showed the highest inhibitory activity for PSMA. As ligand can readily be radiolabeled since its fluorine atom is adjacent to the nitrogen atom of its pyridine ring, the use of this and related compounds as theranostics can be pursued.
摘要
报道了源自2-氨基己二酸的前列腺特异性膜抗原（PSMA）配体的设计与合成，2-氨基己二酸是一种此前未用于构建PSMA配体的结构单元。研究了我们的PSMA配体的连接子长度和N-取代基的影响，并获得了其中五个与PSMA结合的配体的X射线结构。在本文公开的配体中， 对PSMA表现出最高的抑制活性。由于配体 的氟原子与其吡啶环的氮原子相邻，因此易于进行放射性标记，可探索将该化合物及相关化合物用作治疗诊断剂。
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