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乌拉和蒂明的部分蛋白质结合会影响准确的二皮里米丁脱酶 (DPD) 现型

Sebastian A H van den Wildenberg¹, Sylvia A A M Genet¹, Alexander S Streng²

¹Laboratory of Chemical Biology, department of Biomedical Engineering, Eindhoven University of Technology, the Netherlands; Clinical Laboratory, Catharina Hospital Eindhoven, the Netherlands; Expert Center Clinical Chemistry Eindhoven, the Netherlands.

Journal of pharmaceutical and biomedical analysis

|July 27, 2024

概括

优化DPD表型对于甲化疗至关重要. 蛋白沉方法对 uracil 和 thymine 恢复有显著影响,影响了二皮里米丁脱酶 (DPD) 活性评估.

科学领域:

药物基因组学药物基因组学
临床化学临床化学
分析化学分析化学

背景情况:

甲是一种关键的抗代谢物化疗,用于胃肠道癌症.
DPYD基因型鉴定识别了一些DPD缺陷患者,但错过了其他人.
通过血代谢物分析进行DPD表型鉴定,为评估DPD活性提供了一个替代方案.

研究的目的:

评估不同蛋白沉剂对 uracil,thymine,DHU 和 DHT 的恢复的影响.
为了研究这些分析物的蛋白质结合在人体血中.
突出在DPD表型化中需要分析方法优化.

主要方法:

对血样本中蛋白质沉的乙二 (ACN) 与酸 (PCA) 的比较.
使用液态染色体质谱法 (LC-MS) 量化乌拉,氨酸,二氨酸 (DHU) 和二氨酸 (DHT).
超过以评估目标分析物的蛋白质结合.

主要成果:

与ACN沉相比,PCA沉产生了更高的 uracil 和thymine 血度.
乌拉和蒂明在血中显示出显著的蛋白质结合 (60-65%),与DHU和DHT不同.
沉剂的选择极大地影响了 uracil 和 thymine 的测量度.

结论:

蛋白沉方法显著影响DPD表型化结果.
乌拉和胺的显著蛋白质结合需要仔细的分析方法开发.
需要进一步优化分析方法,才能实现统一的DPD表型界限.

关键词:

二皮里米丁脱酶活性蛋白质结合蛋白质结合蛋白质沉蛋白质沉是一种过程.蛋白质超过方法蛋白质超过提米因 (Thymine) 是一个神经元.乌拉是一种酸盐.

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