SYNTHESIS AND BIOLOGICAL ACTIVITY OF A NEW ALL-TRANS-RETINOL METABOLITES

一种新的全反式视黄醇代谢物的合成和生物活性

• 批准号: 8361148
• 负责人: Hector DeLuca
• 金额: $ 0.09万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361148
• 关键词: All-Trans-Retinol; Biological; COSY; Conceptus; Female; Fetal Resorption; Funding; Grant; Growth and Development function; Isomerism; National Center for Research Resources; Physiological Processes; Pregnancy; Principal Investigator; Rattus; Reproduction; Research; Research Infrastructure; Resources; Source; Spectrum Analysis; Tretinoin; United States National Institutes of Health; Vision; Vitamin A; cost; dietary supplements; feeding; metabolic abnormality assessment; novel; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Retinol and its metabolites participate in many physiological processes, such as growth, development, reproduction, cellular differentiation, and vision. Rats fed with retinol-free and all-trans-retinoic acid (atRA)-supplemented diet fail to reproduce. It has been shown that retinol is required no later then day 10 of gestation in order to prevent fetal resorption in the vitamin A deficient, atRA-supplemented (VAD-RAS) female rats. Metabolic studies on all trans retinol in day 10 conceptuses of vitamin A deficient, retinoic acid supplemented rats led to the isolation and identification of a novel metabolite, the isomers of 2-(hydroxymethyl)-3-methyl-5-(2'-oxopropyl)-2,5-dihydrothiophene. In continuation of our biological studies of this metabolite, we synthesized the cis and trans isomers of the metabolite. Configurations of these final isomers as well as their precursors are to be determined by 1H, 1H COSY 2D spectra and 1H NOE difference spectroscopy to compare the isomers with the naturally occurring ones.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 视黄醇及其代谢产物参与许多生理过程，如生长、发育、生殖、细胞分化和视觉。用不含视黄醇和添加全反式维甲酸（atRA）的饲料喂养的大鼠无法繁殖。已经表明，在不晚于妊娠第10天的情况下需要视黄醇，以防止维生素A缺乏、补充atRA（VAD-RAS）的雌性大鼠中的胎儿吸收。对维生素A缺乏、补充维甲酸的大鼠孕10天的全反式视黄醇进行代谢研究，分离并鉴定了一种新的代谢物，即2-（羟甲基）-3-甲基-5-（2 '-氧代丙基）-2，5-二氢噻吩的异构体。在继续我们对该代谢物的生物学研究中，我们合成了该代谢物的顺式和反式异构体。这些最终异构体以及它们的前体的结构将通过1H，1H COSY 2D光谱和1H NOE差谱来确定，以将异构体与天然存在的异构体进行比较。