稳定的烟酰胺核苷-氨基酸缀合物对嘌呤核苷磷酸化酶。
Nicotinamide riboside-amino acid conjugates that are stable to purine nucleoside phosphorylase.
机构信息
Mitchell Cancer Institute, Department of Pharmacology, University of South Alabama, 1660 Springhill Avenue, Mobile, AL 36693, USA.
出版信息
Org Biomol Chem. 2020 Apr 15;18(15):2877-2885. doi: 10.1039/d0ob00134a.
Abstract
The nutraceutical Nicotinamide Riboside (NR), an efficacious biosynthetic precursor to NAD, is readily metabolized by the purine nucleoside phosphorylase (PNP). Access to the PNP-stable versions of NR is difficult because the glycosidic bond of NR is easily cleaved. Unlike NR, NRH, the reduced form of NR, offers sufficient chemical stability to allow the successful functionalisation of the ribosyl-moiety. Here, we report on a series of NRH and NR derived amino acid conjugates, generated in good to excellent yields and show that O5'-esterification prevents the PNP-catalyzed phosphorolysis of these NR prodrugs.
摘要
营养保健品烟酰胺核糖（NR）是烟酰胺腺嘌呤二核苷酸（NAD）的有效生物合成前体，可被嘌呤核苷磷酸化酶（PNP）轻易代谢。由于 NR 的糖苷键很容易被切断，因此难以获得 PNP 稳定版本的 NR。与 NR 不同，NR 的还原形式 NRH 具有足够的化学稳定性，可成功实现核糖部分的功能化。在这里，我们报告了一系列 NRH 和 NR 衍生的氨基酸缀合物，它们以良好到优异的收率生成，并表明 O5'-酯化可防止这些 NR 前药被 PNP 催化的磷酸解。
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