Synthesis and evaluation of novel photoreactive α-amino acid analog carrying acidic and cleavable functions
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- 作者：Nl ; u B. Bongo ; Takenori Tomohiro ; Yasumaru Hatanaka
- 关键词：Acidic α ; -amino acid ; Acylsulfonamide ; Diazirine ; Cleavable ; Photoaffinity labeling
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 出版时间：1 January 2009
- 年：2009
- 卷：19
- 期：1
- 页码：80-82
- 全文大小：502 K
文摘
A novel photoreactive α-amino acid bearing an acidic residue and a cleavable diazirine was developed. To mimic common acidic α-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 Kiapp value of 162 μM, which is slightly higher than the Km 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 α-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 α-amino acid surrogate would be useful as versatile photoreactive building block.