Synthesis and evaluation of novel photoreactive α-amino acid analog carrying acidic and cleavable functions
Synthesis and evaluation of novel photoreactive α-amino acid analog carrying acidic and cleavable functions
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DOI：
10.1016/j.bmcl.2008.11.013
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Hatanaka, Yasumaru
中科院分区：
文献类型：
--
作者：
Bongo, Nlandu B.;Tomohiro, Takenori;Hatanaka, Yasumaru
开发了一种新的具有光反应性的α-氨基酸，其具有酸性残基和可裂解的二氮杂环丙烷。为了模拟常见的酸性α-氨基酸，将残基设计为具有酸性质子并且能够在生理条件下解离的N-酰基磺酰胺。其生物素标记的衍生物与来自金黄色葡萄球菌V8菌株的谷氨酰内肽酶的抑制测定显示Ki（app）值为162 μ M，这略高于常见底物的K-m值。在UV照射下，该衍生物特异性地光标记谷氨酰内肽酶、L-谷氨酸脱氢酶、谷氨酸-乙酸转氨酶和L-谷氨酰胺合成酶，所有酶对酸性α-氨基酸表现出高亲和力。此外，N-酰基磺酰胺基团在经过短暂的N-烷基化后，在温和的碱性溶液中作为可裂解的连接基团发挥作用。这种酸性α-氨基酸替代物的多功能性质或简单结构将可用作通用的光反应性结构单元。(C)2008爱思唯尔有限公司保留所有权利。
A novel photoreactive alpha-amino acid bearing an acidic residue and a cleavable diazirine was developed. To mimic common acidic alpha-amino acids, the residue was designed to be N-acylsulfonamide that possesses an acidic proton and is able to dissociate under the physiological conditions. The inhibition assay of its biotin-tagged derivative with glutamyl endopeptidase from Staphylococcus aureus V8 strain revealed a Ki(app) value of 162 mu M, which is slightly higher than the K-m value of a common substrate. Upon UV irradiation, this derivative specifically photolabeled glutamyl endopeptidase, L-glutamate dehydrogenase, glutamic oxalacetic transaminase, and L-glutamine synthetase, all the enzymes exhibit high affinity toward acidic alpha-amino acids. In addition, N-acylsulfonamide group functioned as a cleavable linker in mild basic solution after a brief N-alkylation. Either the multifunctional nature or the simple structure of this acidic alpha-amino acid surrogate would be useful as versatile photoreactive building block. (C) 2008 Elsevier Ltd. All rights reserved.