Development of biotin-retinoid conjugates as chemical probes for analysis of retinoid function
Development of biotin-retinoid conjugates as chemical probes for analysis of retinoid function
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开发生物素-类维生素A缀合物作为分析类维生素A功能的化学探针
DOI：
10.1016/j.bmcl.2018.06.011
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发表时间：
2018
影响因子：
2.7
通讯作者：
Gronemeyer Hinrich
中科院分区：
文献类型：
--
作者：
Fujii Shinya;Mori Shuichi;Kagechika Hiroyuki;Mendoza Parra Marco Antonio;Gronemeyer Hinrich
本文报道了合成类维甲酸Am580和生物素通过连接体片段连接的偶联物的合理设计、合成和生物学评价。我们发现类维甲酸部分和生物素部分之间的连接亚结构对保持生物活性至关重要。偶联物4与内源性类视黄醇ATRA(1)和亲本化合物Am580(2)在小鼠胚胎癌P19细胞的神经分化中表现出相似的效力，并表现出相同的基因表达诱导模式。它有望成为研究类视黄醛功能的一种有用的探针。该连接体部分的设计原理和构效关系有望为其他核受体配体的生物素偶联物的开发提供帮助。
Herein, we report the rational design, synthesis and biological evaluation of conjugates consisting of the synthetic retinoid Am580 and biotin connected via a linker moiety. We found that the linking substructure between the retinoid part and the biotin part is critical for retaining the biological activity. Conjugate4with a shorter linker showed similar potency to endogenous retinoid ATRA (1) and the parent compound Am580 (2) for neural differentiation of mouse embryotic carcinoma P19 cells, and showed the same pattern of induction of gene expression. It is expected to be useful as a probe for investigations of retinoid function. The design rationale and structure-activity relationship of the linker moiety are expected to be helpful for developing biotin conjugates of other nuclear receptor ligands.