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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 视黄醇及其代谢产物参与多种生理过程，如生长、发育、生殖、细胞分化和视觉等。用不含视黄醇和全反式维甲酸(AtRA)的饲料喂养的大鼠不能繁殖。为了防止维生素A缺乏、全反式维甲酸(VAD-RAS)补充的雌性大鼠的胎儿吸收，研究表明，不迟于妊娠第10天需要视黄醇。维生素A缺乏补充维甲酸大鼠胚胎第10天的全反式视黄醇代谢研究导致分离和鉴定了一种新的代谢物2-(hydroxymethyl)-3-methyl-5-(2‘-oxopropyl)-2，5-dihydrothiophene.的异构体在对该代谢物进行生物学研究的基础上，我们合成了该代谢物的顺式和反式异构体。这些最终异构体及其前体的构型将通过1H，1H COSY 2D谱和1H NOE差谱来确定，以将异构体与自然发生的异构体进行比较。