Synthesis of Nω-Phospho-<span class="smallCaps">lspan>-arginine by Biocatalytic Phosphorylation of <span class="smallCaps">lspan>-Arginine
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- 作者：Dr. Bernhard Schoenenberger ; Agata Wszolek ; Thomas Milesi ; Dr. Henrike Brundiek ; Dr. Markus Obkircher and Dr. Roland Wohlgemuth
- 刊名：ChemCatChem
- 出版年：2017
- 出版时间：January 9, 2017
- 年：2017
- 卷：9
- 期：1
- 页码：121-126
- 全文大小：814K
- ISSN：1867-3899
文摘
The Nω-phospho-<span class="smallCaps">lspan>-arginine energy-buffering system is mainly present in invertebrates for regulating energy requirements when it is highly needed, such as in the flight muscles of an insect or when energy supply fluctuates, as in the medically important protozoa Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major. The lack of availability of this important metabolite was due to a tedious chemical procedure, by which Nω-phospho-<span class="smallCaps">lspan>-arginine was prepared in over 5 reaction steps in a low yield. Therefore, we aimed at improving the synthetic methodology for the preparation of this important metabolite. As site- and enantioselective kinases have been very useful catalysts for biocatalytic phosphorylations in straightforward syntheses of phosphorylated metabolites, a stable and selective arginine kinase has been selected for the selective phosphorylation of <span class="smallCaps">lspan>-arginine. The Arg gene has been cloned and expressed in E. coli and a highly active arginine kinase has been prepared. A simple synthesis of Nω-phospho-<span class="smallCaps">lspan>-arginine has been developed by arginine kinase catalyzed phosphorylation of <span class="smallCaps">lspan>-arginine combined with the recycling of the phosphorylating agent ATP by using the phosphoenolpyruvate/pyruvate kinase system. After standard work-up, the desired product Nω-phospho-<span class="smallCaps">lspan>-arginine was obtained in gram quantities and in one step.